Submissions for variant NM_000231.3(SGCG):c.581T>C (p.Leu194Ser)

gnomAD frequency: 0.00001  dbSNP: rs547818652

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000723533	SCV000331266	pathogenic	not provided	2016-08-08	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000260683	SCV000743661	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2C	2014-10-08	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000260683	SCV001224332	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2C	2024-01-08	criteria provided, single submitter	clinical testing	This sequence change replaces leucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 194 of the SGCG protein (p.Leu194Ser). This variant is present in population databases (rs547818652, gnomAD 0.004%). This missense change has been observed in individuals with limb girdle muscular dystrophy (LGMD) (PMID: 9673983, 19770540). It has also been observed to segregate with disease in related individuals. This variant is also known as p.Leu193Ser. ClinVar contains an entry for this variant (Variation ID: 281085). 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 SGCG function (PMID: 22095924). For these reasons, this variant has been classified as Pathogenic.
Clinical Genetics and Genomics, Karolinska University Hospital	RCV000723533	SCV001449856	likely pathogenic	not provided	2016-06-23	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000260683	SCV002019204	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2C	2022-12-16	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002265721	SCV002547910	pathogenic	Autosomal recessive limb-girdle muscular dystrophy	2022-05-04	criteria provided, single submitter	clinical testing	Variant summary: SGCG c.581T>C (p.Leu194Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 2e-05 in 201962 control chromosomes. c.581T>C has been reported in the literature in multiple individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive. These data indicate that the variant is very likely to be associated with disease. At least one publication reports experimental evidence evaluating an impact on protein function and showed that this variant disturbs the membrane localization of the protein. Six clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics	RCV000260683	SCV004201046	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2C	2024-03-04	criteria provided, single submitter	clinical testing
Counsyl	RCV000260683	SCV000789520	likely pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2C	2017-02-03	no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000723533	SCV001920044	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000723533	SCV001952236	likely pathogenic	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000723533	SCV002036126	pathogenic	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000260683	SCV002086107	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2C	2020-12-01	no assertion criteria provided	clinical testing