Submissions for variant NM_000231.3(SGCG):c.17A>G (p.Tyr6Cys)

gnomAD frequency: 0.00009  dbSNP: rs148041867

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000391225	SCV000345926	uncertain significance	not provided	2016-09-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000690683	SCV000818382	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2C	2022-08-16	criteria provided, single submitter	clinical testing	This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 6 of the SGCG protein (p.Tyr6Cys). This variant is present in population databases (rs148041867, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SGCG-related conditions. ClinVar contains an entry for this variant (Variation ID: 291214). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C25"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Illumina Laboratory Services, Illumina	RCV001110405	SCV001267836	uncertain significance	Sarcoglycanopathy	2017-10-30	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Revvity Omics, Revvity	RCV000690683	SCV003819970	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2C	2022-01-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000391225	SCV003842446	uncertain significance	not provided	2023-03-05	criteria provided, single submitter	clinical testing	Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000690683	SCV003920472	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2C	2021-03-30	criteria provided, single submitter	clinical testing	SGCG NM_000231.2 exon 2 p.Tyr6Cys (c.17A>G): This variant has not been reported in the literature but is present in 0.02% (31/128292) of European alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/variant/13-23777850-A-G). This variant is present in ClinVar (Variation ID:291214). Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Natera, Inc.	RCV000690683	SCV001455341	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2C	2020-09-16	no assertion criteria provided	clinical testing