Submissions for variant NM_000070.3(CAPN3):c.551C>T (p.Thr184Met)

gnomAD frequency: 0.01026  dbSNP: rs35889956

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000116544	SCV000230021	benign	not specified	2016-07-28	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000116544	SCV000301893	likely benign	not specified		criteria provided, single submitter	clinical testing
GeneDx	RCV000116544	SCV000520878	benign	not specified	2016-05-19	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Invitae	RCV000547941	SCV000645505	benign	Autosomal recessive limb-girdle muscular dystrophy type 2A	2024-01-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000547941	SCV001275824	benign	Autosomal recessive limb-girdle muscular dystrophy type 2A	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to rule this variant out of causing disease. Therefore, this variant is classified as benign.
Athena Diagnostics Inc	RCV001288906	SCV001476316	likely benign	not provided	2020-05-15	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000116544	SCV002104106	benign	not specified	2022-02-18	criteria provided, single submitter	clinical testing	Variant summary: CAPN3 c.551C>T (p.Thr184Met) results in a non-conservative amino acid change located in the Peptidase C2, calpain, catalytic domain (IPR001300) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0024 in 251442 control chromosomes, predominantly at a frequency of 0.035 within the African or African-American subpopulation in the gnomAD database, including 13 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 11 fold of the estimated maximal expected allele frequency for a pathogenic variant in CAPN3 causing Limb-Girdle Muscular Dystrophy, Autosomal Recessive phenotype (0.0032), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Six ClinVar submitters have assessed the variant since 2014: five classified the variant as benign and one as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Fulgent Genetics, Fulgent Genetics	RCV002490788	SCV002797931	likely benign	Autosomal recessive limb-girdle muscular dystrophy type 2A; Muscular dystrophy, limb-girdle, autosomal dominant 4	2021-09-20	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000116544	SCV000150499	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Natera, Inc.	RCV000547941	SCV001461308	benign	Autosomal recessive limb-girdle muscular dystrophy type 2A	2020-09-16	no assertion criteria provided	clinical testing