Submissions for variant NM_000070.3(CAPN3):c.2443C>G (p.Leu815Val)

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003236283	SCV003934018	uncertain significance	not specified	2023-05-30	criteria provided, single submitter	clinical testing	Variant summary: CAPN3 c.2443C>G (p.Leu815Val) results in a conservative amino acid change located in the EF-hand domain (IPR002048) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 250166 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2443C>G has been reported in the literature in at least one compound heterozygous and one homozygous individual affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive (e.g., Ganaraja_2022). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication was ascertained in the context of this evaluation (PMID: 35169782). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.
Baylor Genetics	RCV004572890	SCV005059983	likely pathogenic	Muscular dystrophy, limb-girdle, autosomal dominant 4	2024-03-17	criteria provided, single submitter	clinical testing