Submissions for variant NM_000070.3(CAPN3):c.2306G>A (p.Arg769Gln)

gnomAD frequency: 0.00014  dbSNP: rs80338802

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000711017	SCV000331919	pathogenic	not provided	2018-09-14	criteria provided, single submitter	clinical testing
Invitae	RCV000020096	SCV000766725	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2A	2024-01-29	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 769 of the CAPN3 protein (p.Arg769Gln). This variant is present in population databases (rs80338802, gnomAD 0.006%). This missense change has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy (PMID: 7720071, 7762565, 7795603, 9246005, 12461690, 14645990). It is commonly reported in individuals of Amish ancestry (PMID: 9246005). ClinVar contains an entry for this variant (Variation ID: 17613). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on CAPN3 protein function. Experimental studies have shown that this missense change affects CAPN3 function (PMID: 9642272). For these reasons, this variant has been classified as Pathogenic.
Athena Diagnostics Inc	RCV000711017	SCV000841335	pathogenic	not provided	2018-03-22	criteria provided, single submitter	clinical testing
Kariminejad - Najmabadi Pathology & Genetics Center	RCV001814000	SCV001755555	pathogenic	Abnormality of the musculature	2021-07-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000711017	SCV001764949	pathogenic	not provided	2019-12-09	criteria provided, single submitter	clinical testing	Not observed at a significant frequency in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 31980526, 32668095, 31028937, 7762565, 7795603, 9642272, 14645990, 18258189, 19015733, 20301490, 28300015, 25252238, 16650086, 12461690, 9246005, 7720071, 30564623, 23553538)
Revvity Omics, Revvity	RCV000711017	SCV002018045	pathogenic	not provided	2022-12-08	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003473106	SCV004211569	pathogenic	Muscular dystrophy, limb-girdle, autosomal dominant 4	2023-09-11	criteria provided, single submitter	clinical testing
OMIM	RCV000020096	SCV000039467	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2A	1997-07-01	no assertion criteria provided	literature only
GeneReviews	RCV000020096	SCV000040414	not provided	Autosomal recessive limb-girdle muscular dystrophy type 2A		no assertion provided	literature only
Counsyl	RCV000020096	SCV000788465	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2A	2017-04-21	no assertion criteria provided	clinical testing
Natera, Inc.	RCV000020096	SCV001456375	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2A	2020-09-16	no assertion criteria provided	clinical testing