ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.3443T>C (p.Val1148Ala)

gnomAD frequency: 0.00001  dbSNP: rs1908692504
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001752661 SCV001997575 uncertain significance not provided 2020-01-09 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001868523 SCV002182527 uncertain significance Hyperkalemic periodic paralysis 2023-05-23 criteria provided, single submitter clinical testing 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. ClinVar contains an entry for this variant (Variation ID: 1311678). This variant has not been reported in the literature in individuals affected with SCN4A-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 1148 of the SCN4A protein (p.Val1148Ala).
Athena Diagnostics RCV001752661 SCV005622567 uncertain significance not provided 2024-06-06 criteria provided, single submitter clinical testing Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity. (http://gnomad.broadinstitute.org) Polyphen and MutationTaster predict this amino acid change may be damaging to the protein. Computational tools yielded predictions that this variant may interfere with normal RNA splicing.

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