Distal myopathy with posterior leg and anterior hand involvement: genes and variants

Genes linked to Distal myopathy with posterior leg and anterior hand involvement

• 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.

  9 disease-causing and 1,448 uncertain variants in FLNC are linked to Distal myopathy with posterior leg and anterior hand involvement.

Weakly linked (only a few uncertain records): ADCY5.

Where Distal myopathy with posterior leg and anterior hand involvement variants cluster

• FLNC Filamin 17 (positions 1854–1946): 3 of 9 disease-causing changes, 9.8× more than its size predicts.

Known disease-causing variants in Distal myopathy with posterior leg and anterior hand involvement

Which prediction tools work for Distal myopathy with posterior leg and anterior hand involvement

How often each tool ranks a disease-causing variant above a harmless one (AUROC × 100).

• PolyPhen-2: 91 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CATVariant: 87 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 72 out of 100

Same protein, different disease

• Hypertrophic cardiomyopathy is also caused by FLNC variants; they fall mostly in different places as the Distal myopathy with posterior leg and anterior hand involvement variants (10 disease-causing).
• Restrictive cardiomyopathy is also caused by FLNC variants; they fall mostly in different places as the Distal myopathy with posterior leg and anterior hand involvement variants (3 disease-causing).

Diseases related to Distal myopathy with posterior leg and anterior hand involvement

• Hypertrophic cardiomyopathy, also linked to FLNC
• Dilated cardiomyopathy, also linked to FLNC
• Myofibrillar myopathy, also linked to FLNC
• Restrictive cardiomyopathy, also linked to FLNC
• Myopathy, also linked to FLNC
• Nemaline myopathy, also linked to FLNC

Frequently asked questions

Which genes are linked to Distal myopathy with posterior leg and anterior hand involvement?

In CATVariant, Distal myopathy with posterior leg and anterior hand involvement is linked to 1 analyzed protein: FLNC (Filamin-C).

How many genetic variants are linked to Distal myopathy with posterior leg and anterior hand involvement?

1,538 variants: 9 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 1,449 are of uncertain significance or have conflicting reports.

Which uncertain variants in Distal myopathy with posterior leg and anterior hand involvement look disease-causing?

None of the uncertain variants currently reaches the likely-pathogenic range on computable evidence alone.

Which variant effect predictor works best for Distal myopathy with posterior leg and anterior hand involvement?

Among tools not trained on clinical labels, SIFT separates this disease's known disease-causing variants from harmless ones best (AUROC 0.72, based on 8 disease-causing and 97 harmless variants).

About this data

Variant–disease links come from ClinVar, Open Targets and UniProt, pooled from the latest public CATVariant analysis 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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