ClinVar Miner

Submissions for variant NM_000023.4(SGCA):c.115A>G (p.Thr39Ala)

gnomAD frequency: 0.00026  dbSNP: rs540292629
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001000875 SCV001157956 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2D 2018-10-26 criteria provided, single submitter clinical testing The SGCA c.115A>G; p.Thr39Ala variant (rs540292629), to our knowledge, is not reported in the medical literature or gene specific databases. This variant is found in the African population with an allele frequency of 0.063% (15/23,996 alleles) in the Genome Aggregation Database. The threonine at codon 39 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Thr39Ala variant is uncertain at this time.
Labcorp Genetics (formerly Invitae), Labcorp RCV001000875 SCV001419902 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2D 2022-04-29 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 39 of the SGCA protein (p.Thr39Ala). This variant is present in population databases (rs540292629, gnomAD 0.06%). This variant has not been reported in the literature in individuals affected with SGCA-related conditions. ClinVar contains an entry for this variant (Variation ID: 811177). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
Ambry Genetics RCV002549144 SCV003535172 uncertain significance Inborn genetic diseases 2021-07-14 criteria provided, single submitter clinical testing The c.115A>G (p.T39A) alteration is located in exon 2 (coding exon 2) of the SGCA gene. This alteration results from a A to G substitution at nucleotide position 115, causing the threonine (T) at amino acid position 39 to be replaced by an alanine (A). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity RCV001000875 SCV003827590 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2D 2021-11-29 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001000875 SCV003931631 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2D 2023-02-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003479261 SCV004223001 uncertain significance not specified 2023-11-21 criteria provided, single submitter clinical testing Variant summary: SGCA c.115A>G (p.Thr39Ala) results in a non-conservative amino acid change located in the Dystroglycan-type cadherin-like (IPR006644) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 251454 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.115A>G in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. Six submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV001000875 SCV002087548 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2D 2020-02-21 no assertion criteria provided clinical testing

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