ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.1346C>T (p.Ala449Val)

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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 RCV003085521 SCV003463270 uncertain significance Niemann-Pick disease, type C1 2021-09-17 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 449 of the NPC1 protein (p.Ala449Val). The alanine residue is moderately conserved and there is a small physicochemical difference between alanine and valine. This variant is present in population databases (rs372289265, ExAC 0.01%). This variant has not been reported in the literature in individuals with NPC1-related conditions. 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: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV003111623 SCV003799099 uncertain significance not provided 2022-10-11 criteria provided, single submitter clinical testing PM2

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