Submissions for variant NM_000070.3(CAPN3):c.1117T>C (p.Trp373Arg)

dbSNP: rs775453643

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics	RCV000710091	SCV000255647	pathogenic	not provided	2015-07-28	criteria provided, single submitter	clinical testing	Not found in the total gnomAD dataset, and the data is high quality. Assessment of experimental evidence suggests this variant results in abnormal protein function. Segregation with disease in affected individuals from a single family.
Eurofins Ntd Llc (ga)	RCV000710091	SCV000333339	uncertain significance	not provided	2016-12-28	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000201159	SCV000645464	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2A	2024-01-11	criteria provided, single submitter	clinical testing	This sequence change replaces tryptophan, which is neutral and slightly polar, with arginine, which is basic and polar, at codon 373 of the CAPN3 protein (p.Trp373Arg). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with autosomal recessive limb-girdle muscular dystrophy (PMID: 18337726, 30564623; Invitae). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 217145). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Experimental studies have shown that this missense change affects CAPN3 function (PMID: 18258189). For these reasons, this variant has been classified as Pathogenic.
Counsyl	RCV000201159	SCV000800735	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2A	2017-10-10	criteria provided, single submitter	clinical testing
Clinical Genetics and Genomics, Karolinska University Hospital	RCV000710091	SCV001450290	likely pathogenic	not provided	2015-10-29	criteria provided, single submitter	clinical testing
Kariminejad - Najmabadi Pathology & Genetics Center	RCV001814104	SCV001755642	likely pathogenic	Abnormality of the musculature	2021-07-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000710091	SCV002520218	likely pathogenic	not provided	2022-05-23	criteria provided, single submitter	clinical testing	Individual homozygous for the W373R variant was found to have absent CAPN3 protein on western blot (Duno et al., 2008); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 18258189, 16627476, 33281875, 22443334, 18337726, 30564623, 32528171, 27535533, 33726816)
MGZ Medical Genetics Center	RCV000201159	SCV002581630	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2A	2022-07-28	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000710091	SCV003822477	likely pathogenic	not provided	2022-02-07	criteria provided, single submitter	clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens	RCV000201159	SCV004014008	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2A	2023-02-10	criteria provided, single submitter	clinical testing	PM2, PP2, PP3, PP5
Institute of Human Genetics Munich, Klinikum Rechts Der Isar, TU München	RCV000201159	SCV004045895	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2A	2023-07-04	criteria provided, single submitter	clinical testing
Center of Genomic medicine, Geneva, University Hospital of Geneva	RCV000201159	SCV004100670	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2A	2023-03-10	criteria provided, single submitter	clinical testing	This variant was identified in an homozygous state in a patient with limb-girdle muscular dystrophy
CeGaT Center for Human Genetics Tuebingen	RCV000710091	SCV004136422	uncertain significance	not provided	2022-03-01	criteria provided, single submitter	clinical testing	CAPN3: PM2, PM3
Baylor Genetics	RCV003462345	SCV004213777	likely pathogenic	Muscular dystrophy, limb-girdle, autosomal dominant 4	2024-01-05	criteria provided, single submitter	clinical testing
Center for Genomic Medicine, King Faisal Specialist Hospital and Research Center	RCV000201159	SCV004809356	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2A	2024-04-04	criteria provided, single submitter	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000710091	SCV001740459	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000710091	SCV001800018	likely pathogenic	not provided		no assertion criteria provided	clinical testing