ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.2141G>A (p.Arg714His)

gnomAD frequency: 0.00004  dbSNP: rs375047023
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000658803 SCV000780598 uncertain significance not provided 2017-12-01 criteria provided, single submitter clinical testing
Eurofins Ntd Llc (ga) RCV000658803 SCV000862199 uncertain significance not provided 2018-07-05 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001124512 SCV001283477 uncertain significance Niemann-Pick disease, type C1 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae RCV001124512 SCV003299393 uncertain significance Niemann-Pick disease, type C1 2022-09-01 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 714 of the NPC1 protein (p.Arg714His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with NPC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 546815). 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 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.

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