Familial restrictive cardiomyopathy: genes and variants
Explore variant evidence for Familial restrictive cardiomyopathy across 6 analyzed proteins (TNNT2, TNNI3, FLNC, MYH7, TNNC1 and 1 more). Linked ClinVar records include 31 pathogenic or likely pathogenic variants, 136 variants of uncertain significance and 24 with conflicting classifications.
Coverage includes proteins already analyzed in CATVariant, not every gene involved in this condition. Database links are associations, not an assessment of clinical gene–disease validity. Computable evidence prioritizes variants for expert review and does not reclassify them. Source labels are pooled across this disease family.
Data updated 2026-10-21. Automated aggregation, not a clinical review date.
Download variant evidence (CSV)
Genes linked to Familial restrictive cardiomyopathy
TNNT2: Troponin T, cardiac muscle
It anchors the cardiac troponin complex to tropomyosin and helps translate calcium-dependent conformational changes into controlled actin-myosin interaction. Pathogenic variants can cause hypertrophic, dilated, or restrictive cardiomyopathy and alter arrhythmic risk.
16 ClinVar pathogenic / likely pathogenic and 148 uncertain variants in TNNT2 have source records linked to Familial restrictive cardiomyopathy. Association strength is not clinical gene validity.
TNNI3: Troponin I, cardiac muscle
It restrains cardiac actin-myosin interaction at low calcium and shifts position within the troponin complex when calcium binds, allowing contraction. Pathogenic variants can alter thin-filament calcium sensitivity and cause hypertrophic, restrictive, or dilated cardiomyopathy.
11 ClinVar pathogenic / likely pathogenic and 8 uncertain variants in TNNI3 have source records linked to Familial restrictive cardiomyopathy. Association strength is not clinical gene validity.
FLNC: Filamin-C
It crosslinks actin and anchors signaling and structural proteins at Z-discs, costameres, and other mechanically stressed sites in striated muscle. Pathogenic variants can cause arrhythmogenic or dilated cardiomyopathy as well as myofibrillar and distal myopathies.
3 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in FLNC have source records linked to Familial restrictive cardiomyopathy. Association strength is not clinical gene validity.
MYH7: Myosin-7
Its beta-myosin motor converts ATP hydrolysis into force within cardiac and slow-skeletal-muscle sarcomeres. Pathogenic variants are major causes of hypertrophic and dilated cardiomyopathy and can also produce inherited skeletal myopathies.
1 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in MYH7 have source records linked to Familial restrictive cardiomyopathy. Association strength is not clinical gene validity.
TNNC1: Troponin C, slow skeletal and cardiac muscles
It binds calcium during each heartbeat and shifts the troponin complex to permit actin-myosin interaction and force generation in cardiac muscle. Pathogenic variants can alter calcium sensitivity and cause hypertrophic or dilated cardiomyopathy.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in TNNC1 have source records linked to Familial restrictive cardiomyopathy. Association strength is not clinical gene validity.
MYPN: Myopalladin
It links sarcomeric and cytoskeletal proteins at the Z-disc and intercalated-disc regions, helping transmit mechanical force and maintain muscle architecture. Pathogenic variants can cause dilated or hypertrophic cardiomyopathy and, in some cases, skeletal myopathy.
0 ClinVar pathogenic / likely pathogenic and 0 uncertain variants in MYPN have source records linked to Familial restrictive cardiomyopathy. Association strength is not clinical gene validity.
Weakly linked (only a few uncertain records): MYH6, DSP, MYL2 and MYL3.
Where Familial restrictive cardiomyopathy variants cluster
- TNNI3 Involved in binding TNC and actin (positions 129–149): 5 of 11 ClinVar pathogenic / likely pathogenic variants, 4.5× more than its size predicts.
ClinVar pathogenic and likely pathogenic variants linked to Familial restrictive cardiomyopathy
| Variant | Position | Protein part | Clinical label |
|---|---|---|---|
| TNNI3 R145Q | 145 | Involved in binding TNC and actin | Pathogenic / likely pathogenic (★★) |
| TNNI3 R145W | 145 | Involved in binding TNC and actin | Pathogenic / likely pathogenic (★★) |
| TNNT2 I89N | 89 | Pathogenic / likely pathogenic (★★) | |
| TNNT2 R141Q | 141 | Pathogenic / likely pathogenic (★★) | |
| TNNI3 R141W | 141 | Involved in binding TNC and actin | Pathogenic / likely pathogenic (★★) |
| TNNT2 R141P | 141 | Pathogenic / likely pathogenic (★★) | |
| MYH7 G768R | 768 | Myosin motor | Pathogenic / likely pathogenic (★★) |
| TNNI3 R141Q | 141 | Involved in binding TNC and actin | Pathogenic / likely pathogenic (★★) |
| TNNI3 R170Q | 170 | Pathogenic / likely pathogenic (★★) | |
| TNNI3 R170W | 170 | Pathogenic / likely pathogenic (★★) | |
| TNNT2 G92R | 92 | Pathogenic / likely pathogenic (★★) | |
| TNNT2 I100N | 100 | Pathogenic / likely pathogenic (★★) | |
| TNNT2 R144G | 144 | Pathogenic / likely pathogenic (★★) | |
| TNNT2 F120L | 120 | Pathogenic / likely pathogenic (★★) | |
| TNNI3 K178E | 178 | Pathogenic / likely pathogenic (★★) | |
| TNNT2 R102Q | 102 | Pathogenic / likely pathogenic (★★) | |
| TNNT2 R183W | 183 | Pathogenic / likely pathogenic (★★) | |
| TNNT2 I89F | 89 | Pathogenic / likely pathogenic (★) | |
| TNNT2 D96Y | 96 | Pathogenic / likely pathogenic (★) | |
| TNNT2 V95M | 95 | Pathogenic / likely pathogenic (★) | |
| TNNT2 F97L | 97 | Pathogenic / likely pathogenic (★) | |
| FLNC P2298S | 2298 | Filamin 20 | Pathogenic / likely pathogenic (★) |
| TNNT2 K107N | 107 | Pathogenic / likely pathogenic (★) | |
| FLNC Y2563C | 2563 | Filamin 23 | Pathogenic / likely pathogenic (★) |
| TNNT2 S189A | 189 | Pathogenic / likely pathogenic (★) | |
| TNNI3 S44A | 44 | Involved in binding TNC | Pathogenic / likely pathogenic (★) |
| TNNT2 V85M | 85 | Pathogenic / likely pathogenic (★) | |
| TNNI3 L144Q | 144 | Involved in binding TNC and actin | Pathogenic / likely pathogenic |
| FLNC I1621F | 1621 | Filamin 14 | Pathogenic / likely pathogenic |
| TNNI3 D190G | 190 | Pathogenic / likely pathogenic | |
| TNNI3 D127Y | 127 | Pathogenic / likely pathogenic |
Uncertain variants prioritized for review in Familial restrictive cardiomyopathy
| Variant | Position | Protein part | Clinical label | Evidence |
|---|---|---|---|---|
| TNNT2 R144P | 144 | Conflicting reports (★) | +6: 3 other pathogenic changes within 3 positions; R144G at the same position is pathogenic; REVEL 0.893 | |
| TNNT2 R144Q | 144 | Conflicting reports (★) | +6: 3 other pathogenic changes within 3 positions; R144G at the same position is pathogenic; REVEL 0.858 | |
| TNNT2 R144W | 144 | Uncertain (★★) | +6: 3 other pathogenic changes within 3 positions; R144G at the same position is pathogenic; REVEL 0.796 |
Which prediction tools work for Familial restrictive cardiomyopathy
Observed separation of ClinVar pathogenic / likely pathogenic from benign / likely benign variants (AUROC × 100). This benchmark is not a clinical recommendation.
- MetaLR: 97 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- MetaSVM: 96 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CATVariant: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- REVEL: 90 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- AlphaMissense: 88 out of 100
- PolyPhen-2: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- CADD: 86 out of 100
- ESM1b (LLR): 83 out of 100
- SIFT: 83 out of 100
- MutPred2: 63 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- EVE: 57 out of 100
- SpliceAI: 56 out of 100 (learned from overlapping clinical labels, so this is optimistic)
- phyloP: 52 out of 100
- Pangolin: 38 out of 100 (learned from overlapping clinical labels, so this is optimistic)
Same protein, different disease
- Hypertrophic cardiomyopathy also has ClinVar records linked to TNNT2 variants; they fall in the same places as the Familial restrictive cardiomyopathy variants (20 pathogenic / likely pathogenic).
- Dilated cardiomyopathy also has ClinVar records linked to TNNT2 variants; they fall in the same places as the Familial restrictive cardiomyopathy variants (18 pathogenic / likely pathogenic).
- Primary dilated cardiomyopathy also has ClinVar records linked to TNNT2 variants; they fall mostly in different places as the Familial restrictive cardiomyopathy variants (7 pathogenic / likely pathogenic).
- Familial isolated dilated cardiomyopathy also has ClinVar records linked to TNNT2 variants; they fall mostly in different places as the Familial restrictive cardiomyopathy variants (3 pathogenic / likely pathogenic).
- Hypertrophic cardiomyopathy also has ClinVar records linked to TNNI3 variants; they fall partly in the same places as the Familial restrictive cardiomyopathy variants (24 pathogenic / likely pathogenic).
- Dilated cardiomyopathy 1FF also has ClinVar records linked to TNNI3 variants; they fall mostly in different places as the Familial restrictive cardiomyopathy variants (7 pathogenic / likely pathogenic).
- Hypertrophic cardiomyopathy also has ClinVar records linked to FLNC variants; they fall mostly in different places as the Familial restrictive cardiomyopathy variants (10 pathogenic / likely pathogenic).
- Distal myopathy with posterior leg and anterior hand involvement also has ClinVar records linked to FLNC variants; they fall mostly in different places as the Familial restrictive cardiomyopathy variants (9 pathogenic / likely pathogenic).
- Myofibrillar myopathy also has ClinVar records linked to FLNC variants; they fall mostly in different places as the Familial restrictive cardiomyopathy variants (7 pathogenic / likely pathogenic).
- Hypertrophic cardiomyopathy also has ClinVar records linked to MYH7 variants; they fall mostly in different places as the Familial restrictive cardiomyopathy variants (239 pathogenic / likely pathogenic).
- Dilated cardiomyopathy also has ClinVar records linked to MYH7 variants; they fall mostly in different places as the Familial restrictive cardiomyopathy variants (21 pathogenic / likely pathogenic).
- Primary dilated cardiomyopathy also has ClinVar records linked to MYH7 variants; they fall mostly in different places as the Familial restrictive cardiomyopathy variants (15 pathogenic / likely pathogenic).
- Hyaline body myopathy also has ClinVar records linked to MYH7 variants; they fall mostly in different places as the Familial restrictive cardiomyopathy variants (13 pathogenic / likely pathogenic).
- Laing early-onset distal myopathy also has ClinVar records linked to MYH7 variants; they fall mostly in different places as the Familial restrictive cardiomyopathy variants (7 pathogenic / likely pathogenic).
Diseases related to Familial restrictive cardiomyopathy
- Hypertrophic cardiomyopathy, also linked to FLNC, MYH7, MYPN, TNNC1 and 2 more
- Dilated cardiomyopathy, also linked to FLNC, MYH7, TNNC1, TNNI3 and 1 more
- Familial isolated dilated cardiomyopathy, also linked to MYH7, MYPN, TNNC1, TNNI3 and 1 more
- Primary dilated cardiomyopathy, also linked to MYH7, MYPN, TNNI3 and TNNT2
- Primary familial hypertrophic cardiomyopathy, also linked to MYH7 and TNNI3
- Left ventricular noncompaction, also linked to MYH7 and TNNT2
- Primary familial dilated cardiomyopathy, also linked to MYH7 and TNNT2
- Dilated cardiomyopathy 1FF, also linked to TNNC1 and TNNI3
- Myopathy, also linked to FLNC and MYH7
- Myofibrillar myopathy, also linked to FLNC
- Arrhythmogenic right ventricular dysplasia, also linked to MYH7
- Hyaline body myopathy, also linked to MYH7
Frequently asked questions
Which genes have records linked to Familial restrictive cardiomyopathy?
This view contains 6 analyzed proteins: TNNT2, TNNI3, FLNC, MYH7, TNNC1 and 1 more. Links come from clinical records and association databases. They do not imply that every listed gene is a validated cause, and missing genes may not yet be analyzed.
What do the clinical classifications mean?
Linked records include 31 pathogenic or likely pathogenic variants, 136 variants of uncertain significance and 24 with conflicting classifications. Labels summarize source records; multi-condition records may not make a separate assertion for this disease. Check the original record and review status.
Does the evidence score change a VUS classification?
No. 3 VUS or conflicting variants reach the likely-pathogenic points range on the computable criteria available here. This is a research prioritization signal, not a clinical classification. Patient, family and other required evidence may be missing.
Can I download the variant evidence?
Download the CSV for all 233 variants in the selected disease scope, including clinical labels, review status, evidence criteria, predictor scores, functional measurements and population frequency where available.
About this data
Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from eligible public CATVariant analyses of each human protein. Evidence scores use the ACMG/AMP Bayesian points scale with computable criteria only (position among known disease variants, rarity in gnomAD, calibrated predictors, deep mutational scanning); there is no family or patient data, so they prioritise variants for expert review and never classify them.
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