ClinVar Miner

Submissions for variant NM_133642.5(LARGE1):c.2255C>G (p.Ala752Gly)

gnomAD frequency: 0.00006  dbSNP: rs200024875
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000149996 SCV000196855 uncertain significance not provided 2017-08-14 criteria provided, single submitter clinical testing The A752G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is conserved across species. However, the A752G variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001212199 SCV001383775 uncertain significance Muscular dystrophy-dystroglycanopathy type B6 2022-07-19 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 752 of the LARGE1 protein (p.Ala752Gly). This variant is present in population databases (rs200024875, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with LARGE1-related conditions. ClinVar contains an entry for this variant (Variation ID: 162585). 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.
Revvity Omics, Revvity RCV000149996 SCV003816437 uncertain significance not provided 2019-04-27 criteria provided, single submitter clinical testing

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