ClinVar Miner

Submissions for variant NM_000231.3(SGCG):c.579-2A>G

gnomAD frequency: 0.00001  dbSNP: rs754415994
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000441409 SCV000535827 pathogenic not provided 2017-07-10 criteria provided, single submitter clinical testing The c.579-2 A>G pathogenic variant in the SGCG gene destroys the canonical splice acceptor site in intron 6. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.579-2 A>G variant is not observed at significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Although the c.579-2 A>G variant has not been published to our knowledge, other splice site variants in the SGCG gene have been reported in the Human Gene Mutation Database in association with limb-girdle muscular dystrophy (Stenson et al., 2014).
Counsyl RCV000673462 SCV000798666 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2C 2018-03-16 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000673462 SCV002270979 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2C 2021-03-08 criteria provided, single submitter clinical testing In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with SGCG-related conditions. ClinVar contains an entry for this variant (Variation ID: 392545). This variant is present in population databases (rs754415994, ExAC 0.006%). This sequence change affects an acceptor splice site in intron 6 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).
Baylor Genetics RCV000673462 SCV004201039 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2C 2023-09-07 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000673462 SCV004238355 pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2C 2023-02-14 criteria provided, single submitter clinical testing

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