ClinVar Miner

Submissions for variant NM_000426.4(LAMA2):c.8969T>G (p.Ile2990Ser)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003095772 SCV003485348 uncertain significance LAMA2-related muscular dystrophy 2022-04-11 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 2990 of the LAMA2 protein (p.Ile2990Ser). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with LAMA2-related conditions. 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 not expected to disrupt LAMA2 protein function. 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003994499 SCV004813585 uncertain significance not specified 2024-02-21 criteria provided, single submitter clinical testing Variant summary: LAMA2 c.8969T>G (p.Ile2990Ser) results in a non-conservative amino acid change located in the Laminin G domain (IPR001791) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251232 control chromosomes (gnomAD database v4.0.0). 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.8969T>G in individuals affected with Laminin Alpha 2-Related Dystrophy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2171464). Based on the evidence outlined above, the variant was classified as uncertain significance.

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