ClinVar Miner

Submissions for variant NM_001130987.2(DYSF):c.2929C>T (p.Arg977Trp)

gnomAD frequency: 0.00002  dbSNP: rs202218890
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000725415 SCV000336807 pathogenic not provided 2015-11-10 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000763505 SCV000894295 pathogenic Miyoshi muscular dystrophy 1; Autosomal recessive limb-girdle muscular dystrophy type 2B; Distal myopathy with anterior tibial onset 2021-10-06 criteria provided, single submitter clinical testing
Invitae RCV000791498 SCV000930750 pathogenic Qualitative or quantitative defects of dysferlin 2023-12-19 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 959 of the DYSF protein (p.Arg959Trp). This variant is present in population databases (rs202218890, gnomAD 0.006%). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy and Myoshi myopathy (PMID: 14678801, 16934466, 17070050, 19528035, 21522182, 22194990). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 284254). 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) performed at Invitae indicates that this missense variant is expected to disrupt DYSF protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic.
CeGaT Center for Human Genetics Tuebingen RCV000725415 SCV001247518 pathogenic not provided 2023-02-01 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV000725415 SCV001713177 pathogenic not provided 2020-05-28 criteria provided, single submitter clinical testing PS3, PS4_moderate, PM2, PP1, PP4
Revvity Omics, Revvity Omics RCV000725415 SCV002022159 pathogenic not provided 2020-11-18 criteria provided, single submitter clinical testing
GeneDx RCV000725415 SCV004034580 pathogenic not provided 2023-09-05 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 19528035, 26806107, 22194990, 14678801, 17994539, 16100712, 21522182, 17070050, 30028523, 31130284, 34426522, 31589614, 33258288, 32528171, 33715265, 33610434, 35175440, 34559919, 24438169)
Preventiongenetics, part of Exact Sciences RCV003401245 SCV004119160 pathogenic DYSF-related condition 2023-10-03 criteria provided, single submitter clinical testing The DYSF c.2875C>T variant is predicted to result in the amino acid substitution p.Arg959Trp. This variant has been repeatedly reported in individuals with autosomal recessive dysferlinopathy; immunohistochemistry assays for these patients have demonstrated severely reduced to an absence of dysferlin protein expression (see Cagliani et al. 2003. PubMed ID: 14678801; Klinge et al. 2009. PubMed ID: 19528035; Gallardo et al. 2011. PubMed ID: 22194990; Arrigoni et al. 2018. PubMed ID: 30028523; Fanin et al. 2006. PubMed ID: 16934466; Guglieri et al. 2008. PubMed ID: 17994539; De Luna et al. 2006. PubMed ID: 17070050). This variant is reported in 0.0070% of alleles in individuals of European (non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-71797014-C-T). Taken together, this variant is interpreted as pathogenic.
Baylor Genetics RCV003469231 SCV004194156 pathogenic Miyoshi muscular dystrophy 1 2023-10-31 criteria provided, single submitter clinical testing
Counsyl RCV000262612 SCV000788615 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2B 2017-04-28 no assertion criteria provided clinical testing
Natera, Inc. RCV000262612 SCV002082244 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2B 2020-09-04 no assertion criteria provided clinical testing

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