Congenital myotonia, autosomal recessive form: genes and variants

Genes linked to Congenital myotonia, autosomal recessive form

• CLCN1: Chloride channel protein 1

  Its chloride conductance stabilizes the resting membrane potential of skeletal muscle and prevents repetitive firing after contraction. Loss-of-function variants cause myotonia congenita, with delayed muscle relaxation and stiffness.

  90 disease-causing and 453 uncertain variants in CLCN1 are linked to Congenital myotonia, autosomal recessive form.

Where Congenital myotonia, autosomal recessive form variants cluster

• CLCN1 Helical (positions 483–498): 7 of 90 disease-causing changes, 4.8× more than its size predicts.
• CLCN1 Helical (positions 281–290): 5 of 90 disease-causing changes, 5.5× more than its size predicts.
• CLCN1 Transmembrane (positions 302–321): 7 of 90 disease-causing changes, 3.8× more than its size predicts.
• CLCN1 Note=Loop between two helices (positions 415–418): 3 of 90 disease-causing changes, 8.2× more than its size predicts.
• CLCN1 Helical (positions 541–554): 5 of 90 disease-causing changes, 3.9× more than its size predicts.

Known disease-causing variants in Congenital myotonia, autosomal recessive form

Showing 60 of 90.

Uncertain variants in Congenital myotonia, autosomal recessive form that look disease-causing

Which prediction tools work for Congenital myotonia, autosomal recessive form

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

• REVEL: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• CADD: 99 out of 100
• CATVariant: 99 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• SIFT: 97 out of 100
• PolyPhen-2: 95 out of 100 (learned from overlapping clinical labels, so this is optimistic)
• phyloP: 91 out of 100

Same protein, different disease

• Skeletal muscle channelopathy is also caused by CLCN1 variants; they fall in the same places as the Congenital myotonia, autosomal recessive form variants (11 disease-causing).

Diseases related to Congenital myotonia, autosomal recessive form

• Congenital myotonia, autosomal dominant form, also linked to CLCN1
• Hyperkalemic periodic paralysis, also linked to CLCN1
• Hypokalemic periodic paralysis, also linked to CLCN1
• Skeletal muscle channelopathy, also linked to CLCN1
• Batten-Turner congenital myopathy, also linked to CLCN1

Frequently asked questions

Which genes are linked to Congenital myotonia, autosomal recessive form?

In CATVariant, Congenital myotonia, autosomal recessive form is linked to 1 analyzed protein: CLCN1 (Chloride channel protein 1).

How many genetic variants are linked to Congenital myotonia, autosomal recessive form?

555 variants: 90 are classified as disease-causing (pathogenic or likely pathogenic) in ClinVar and 453 are of uncertain significance or have conflicting reports.

Which uncertain variants in Congenital myotonia, autosomal recessive form look disease-causing?

19 uncertain variants reach the likely-pathogenic range of the ACMG/AMP points scale on computable evidence, for example CLCN1 G355E, CLCN1 G482E, CLCN1 A566V, CLCN1 G285R and CLCN1 I527T. These are leads for expert review, not diagnoses.

Which variant effect predictor works best for Congenital myotonia, autosomal recessive form?

Among tools not trained on clinical labels, CADD separates this disease's known disease-causing variants from harmless ones best (AUROC 0.99, based on 66 disease-causing and 13 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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