ClinVar Miner

Submissions for variant NM_001164508.2(NEB):c.9178A>G (p.Met3060Val)

gnomAD frequency: 0.00021  dbSNP: rs538524863
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000532653 SCV000640893 uncertain significance Nemaline myopathy 2 2022-07-30 criteria provided, single submitter clinical testing This sequence change replaces methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 3060 of the NEB protein (p.Met3060Val). This variant is present in population databases (rs538524863, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with NEB-related conditions. ClinVar contains an entry for this variant (Variation ID: 465650). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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 RCV004701625 SCV005203890 uncertain significance not specified 2024-07-02 criteria provided, single submitter clinical testing Variant summary: NEB c.9178A>G (p.Met3060Val) results in a conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00038 in 249242 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in NEB causing Nemaline Myopathy 2 (0.00038 vs 0.0035), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.9178A>G in individuals affected with Nemaline Myopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 465650). Based on the evidence outlined above, the variant was classified as uncertain significance.
Natera, Inc. RCV000532653 SCV002077173 uncertain significance Nemaline myopathy 2 2019-11-11 no assertion criteria provided clinical testing

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