ClinVar Miner

Submissions for variant NM_000231.3(SGCG):c.848G>A (p.Cys283Tyr)

dbSNP: rs104894422
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000002083 SCV000634392 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2C 2024-03-17 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 283 of the SGCG protein (p.Cys283Tyr). This variant is present in population databases (rs104894422, gnomAD 0.0009%). This missense change has been observed in individual(s) with limb-girdle muscular dystrophy type 2C (PMID: 8968757, 9781048, 22095924). It is commonly reported in individuals of Roma ancestry (PMID: 10447257, 15322984). ClinVar contains an entry for this variant (Variation ID: 2006). 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 SGCG protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects SGCG function (PMID: 22095924). For these reasons, this variant has been classified as Pathogenic.
Fulgent Genetics, Fulgent Genetics RCV000002083 SCV000893320 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2C 2018-10-31 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV000002083 SCV001164490 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2C 2018-12-03 criteria provided, single submitter research The homozygous p.Cys283Tyr variant in SGCG was identified by our study in one individual with limb-girdle muscular dystrophy (LGMD). This variant has been identified in 0.0008957% (1/111646) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs104894422). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that this variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In vitro functional studies provide some evidence that the p.Cys283Tyr variant may impact protein function by disrupting sarcoglycan formation and protein localization to the membrane (PMID: 14981741, 22095924). However, these types of assays may not accurately represent biological function. The p.Cys283Tyr variant in SGCG has been reported in at least 327 Spanish Gypsy individuals with LGMD, segregated with disease in 13 affected relatives from 2 families, and is believed to be a founder variant (PMID: 9781048, 20345928, 9658457, 22095924). In summary, the p.Cys283Tyr variant is pathogenic. ACMG/AMP Criteria applied: PM2, PP3, PS3, PP1_Strong (Richards 2015).
CeGaT Center for Human Genetics Tuebingen RCV001090241 SCV001245660 pathogenic not provided 2019-05-01 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000002083 SCV003827897 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2C 2023-03-15 criteria provided, single submitter clinical testing
Baylor Genetics RCV000002083 SCV004201052 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2C 2023-06-05 criteria provided, single submitter clinical testing
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000002083 SCV005051956 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2C 2024-02-01 criteria provided, single submitter curation
OMIM RCV000002083 SCV000022241 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2C 2004-11-01 no assertion criteria provided literature only
Natera, Inc. RCV000002083 SCV002086117 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2C 2020-12-23 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.