Submissions for variant NM_000070.3(CAPN3):c.2279dup (p.Asn760fs)

dbSNP: rs775130589

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000790763	SCV000343367	pathogenic	not provided	2016-07-01	criteria provided, single submitter	clinical testing	The c.2279dupA CAPN3 pathogenic variant has been reported in individuals with LGMD2A1,2 and is of a type expected to cause disease. 1. Groen et al. Brain. 2007 Dec;130(Pt 12):3237-49. 2. www.lovd.nl/CAPN3 AKT 7-1-16
Counsyl	RCV000399324	SCV000795555	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2A	2017-11-09	criteria provided, single submitter	clinical testing
Invitae	RCV000399324	SCV001581543	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2A	2023-07-11	criteria provided, single submitter	clinical testing	This premature translational stop signal has been observed in individual(s) with autosomal recessive limb girdle muscular dystrophy (PMID: 18055493). This variant is also known as c.2278insA. ClinVar contains an entry for this variant (Variation ID: 289082). For these reasons, this variant has been classified as Pathogenic. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Asn760Lysfs*5) in the CAPN3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CAPN3 are known to be pathogenic (PMID: 10330340, 15689361).
Revvity Omics, Revvity	RCV000790763	SCV002018089	pathogenic	not provided	2021-10-12	criteria provided, single submitter	clinical testing
GeneDx	RCV000790763	SCV002759049	likely pathogenic	not provided	2022-05-25	criteria provided, single submitter	clinical testing	Observed with a pathogenic variant (p.Arg490Trp) in a patient in the published literature with Limb-girdle muscular dystrophy, but it is unknown whether the variants occurred on the same allele (in cis) or on different alleles (in trans) (Groen et al., 2007); Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 18055493)
PreventionGenetics, part of Exact Sciences	RCV003401267	SCV004105875	pathogenic	CAPN3-related condition	2023-04-28	criteria provided, single submitter	clinical testing	The CAPN3 c.2279dupA variant is predicted to result in a frameshift and premature protein termination (p.Asn760Lysfs*5). This variant was reported in the compound heterozygous state in an individual with limb-girdle muscular dystrophy 2A (Groen et al 2007. PubMed ID: 18055493). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/15-42703095-C-CA). Frameshift variants in CAPN3 are expected to be pathogenic. This variant is interpreted as pathogenic.