ClinVar Miner

Submissions for variant NM_000334.4(SCN4A):c.4300T>C (p.Ser1434Pro) (rs1567816549)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000685540 SCV000813025 likely pathogenic Hyperkalemic Periodic Paralysis Type 1 2018-06-01 criteria provided, single submitter clinical testing This sequence change replaces serine with proline at codon 1434 of the SCN4A protein (p.Ser1434Pro). The serine residue is highly conserved and there is a moderate physicochemical difference between serine and proline. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals affected with paramyotonia congenita (PMID: 23771340, Invitae), and has also been observed to segregate with paramyotonia congenita in a family (PMID: 29111379). 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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