ClinVar Miner

Submissions for variant NM_000070.3(CAPN3):c.1681T>C (p.Tyr561His)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003112307 SCV003787016 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2A 2022-07-26 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy (PMID: 31410652). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with histidine, which is basic and polar, at codon 561 of the CAPN3 protein (p.Tyr561His).
Biomedical Genomics and Oncogenetics Laboratory, Institut Pasteur de Tunis, University Tunis El Manar RCV003112307 SCV004012901 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2A 2023-07-13 criteria provided, single submitter research We have identified this mutation in a Tunisian patient with an individual comorbidity of Bathing Suit Ichthyosis and LGMD2A which is the first case worldwide with the co-occurrence of these two ultra-rare diseases. The muscle impairment was particularly severe in the postpartum period. This mutation was already reported in another Tunisian patient with a progressive weakness of lower limbs who became wheelchair-bound at the age of 54 and bedridden at the age of 60(Rekik et al., 2019). The functional evidence of the variant was supported by an Immunohistochemical examination and Western-Blot analysis in the study of Rekik et al., 2019.

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