ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.3001A>G (p.Met1001Val)

dbSNP: rs2058666849
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001327013 SCV001518071 pathogenic Niemann-Pick disease, type C1 2022-10-17 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Met1001 amino acid residue in NPC1. Other variant(s) that disrupt this residue have been observed in individuals with NPC1-related conditions (PMID: 23773996), which suggests that this may be a clinically significant amino acid residue. 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 tolerated. ClinVar contains an entry for this variant (Variation ID: 1026548). This missense change has been observed in individual(s) with Niemann-Pick disease type C (PMID: 23487299, 26981555; 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 methionine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 1001 of the NPC1 protein (p.Met1001Val).
GeneDx RCV004719134 SCV005324821 likely pathogenic not provided 2024-03-12 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23487299, 26869201, 26981555, 23433426)
Natera, Inc. RCV001327013 SCV002095174 uncertain significance Niemann-Pick disease, type C1 2020-07-08 no assertion criteria provided clinical testing

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