ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.1039G>A (p.Val347Ile)

gnomAD frequency: 0.00001  dbSNP: rs376741451
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000728698 SCV000856303 uncertain significance not provided 2017-08-11 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001578731 SCV001806026 uncertain significance Niemann-Pick disease, type C1 2021-07-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001578731 SCV003261586 uncertain significance Niemann-Pick disease, type C1 2022-03-11 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 347 of the NPC1 protein (p.Val347Ile). This variant is present in population databases (rs376741451, gnomAD 0.005%). 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: 593604). 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 not 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.
PreventionGenetics, part of Exact Sciences RCV004748925 SCV005357640 uncertain significance NPC1-related disorder 2024-05-08 no assertion criteria provided clinical testing The NPC1 c.1039G>A variant is predicted to result in the amino acid substitution p.Val347Ile. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0050% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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