ClinVar Miner

Submissions for variant NM_000023.4(SGCA):c.190G>A (p.Ala64Thr)

gnomAD frequency: 0.00001  dbSNP: rs759692350
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000274092 SCV000345600 uncertain significance not provided 2016-08-24 criteria provided, single submitter clinical testing
Invitae RCV001859727 SCV002138943 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2D 2024-01-15 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 64 of the SGCA protein (p.Ala64Thr). This variant is present in population databases (rs759692350, gnomAD 0.01%). This missense change has been observed in individual(s) with clinical features of SGCA-related conditions (PMID: 30218921; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 290930). 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 SGCA protein function with a positive predictive value of 95%. 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.
Revvity Omics, Revvity RCV001859727 SCV003827573 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2D 2024-01-03 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001859727 SCV003931641 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2D 2023-02-08 criteria provided, single submitter clinical testing
Neuberg Centre For Genomic Medicine, NCGM RCV001859727 SCV004048017 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2D criteria provided, single submitter clinical testing The missense variant c.190G>A (p.Ala64Thr) in SGCA gene has been submitted to ClinVar as a Variant of Uncertain Significance, but no details are available for independent assessment. It has not been reported in affected individuals. This variant is reported with the allele frequency (0.001%) in the gnomAD and novel in 1000 genome database. The amino acid Ala at position 64 is changed to a Thr changing protein sequence and it might alter its composition and physico-chemical properties. The amino acid change p.Ala64Thr in SGCA is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. For these reasons, this variant has been classified as Variant of Uncertain Significance (VUS).
Baylor Genetics RCV001859727 SCV004203162 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2D 2024-02-23 criteria provided, single submitter clinical testing

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