ClinVar Miner

Submissions for variant NM_000231.3(SGCG):c.195+1G>C

gnomAD frequency: 0.00004  dbSNP: rs200502077
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000725317 SCV000335981 pathogenic not provided 2015-10-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000340955 SCV001591340 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2C 2023-11-19 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 2 of the SGCG gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in SGCG are known to be pathogenic (PMID: 18285821). This variant is present in population databases (rs200502077, gnomAD 0.02%). Disruption of this splice site has been observed in individuals with clinical features of limb-girdle muscular dystrophy (PMID: 27708273, 31517061). ClinVar contains an entry for this variant (Variation ID: 283707). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001553764 SCV001774758 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy 2021-07-19 criteria provided, single submitter clinical testing Variant summary: SGCG c.195+1G>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 5 splicing donor site. Two predict the variant creates a 3 acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 1.6e-05 in 251302 control chromosomes (gnomAD). c.195+1G>C has been reported in the literature in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive (Reddy_2017). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic (n=2) and likely pathogenic (n=1). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics RCV000340955 SCV004201041 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2C 2023-09-06 criteria provided, single submitter clinical testing
Counsyl RCV000340955 SCV000798829 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2C 2018-03-26 no assertion criteria provided clinical testing

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