ClinVar Miner

Submissions for variant NM_000426.4(LAMA2):c.1792G>A (p.Val598Ile)

gnomAD frequency: 0.00001  dbSNP: rs753232836
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000493458 SCV000583074 uncertain significance not provided 2017-05-24 criteria provided, single submitter clinical testing The V598I variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The V598I variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position where amino acids with similar properties to Valine are tolerated across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function.
Labcorp Genetics (formerly Invitae), Labcorp RCV000806947 SCV000946971 uncertain significance LAMA2-related muscular dystrophy 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces valine with isoleucine at codon 598 of the LAMA2 protein (p.Val598Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is present in population databases (rs753232836, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with LAMA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 430300). 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.

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