ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.1550T>A (p.Val517Glu)

dbSNP: rs2145446753
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001971644 SCV002261342 likely pathogenic Niemann-Pick disease, type C1 2022-03-03 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with Niemann-Pick disease type C (Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces valine, which is neutral and non-polar, with glutamic acid, which is acidic and polar, at codon 517 of the NPC1 protein (p.Val517Glu). 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 expected to disrupt NPC1 protein function. 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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