ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.1221G>C (p.Gln407His)

gnomAD frequency: 0.00003  dbSNP: rs765539977
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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) RCV000301054 SCV000331090 uncertain significance not provided 2018-03-14 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000765408 SCV000896688 uncertain significance Niemann-Pick disease, type C1 2018-10-31 criteria provided, single submitter clinical testing
Invitae RCV000765408 SCV001554711 uncertain significance Niemann-Pick disease, type C1 2022-10-20 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 407 of the NPC1 protein (p.Gln407His). This variant is present in population databases (rs765539977, gnomAD 0.06%). 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: 281031). 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.
Natera, Inc. RCV000765408 SCV002095213 uncertain significance Niemann-Pick disease, type C1 2020-01-24 no assertion criteria provided clinical testing

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