ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3035G>A (p.Gly1012Asp)

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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 RCV003501734 SCV004296920 likely pathogenic Niemann-Pick disease, type C1 2023-02-28 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with aspartic acid, which is acidic and polar, at codon 1012 of the NPC1 protein (p.Gly1012Asp). This missense change has been observed in individual(s) with Niemann-Pick disease type C (PMID: 11545687). 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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