ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.2275A>G (p.Thr759Ala)

gnomAD frequency: 0.00004  dbSNP: rs776873102
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000303121 SCV000342100 uncertain significance not provided 2016-05-12 criteria provided, single submitter clinical testing
Invitae RCV001855198 SCV002172149 uncertain significance Niemann-Pick disease, type C1 2022-07-13 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with alanine, which is neutral and non-polar, at codon 759 of the NPC1 protein (p.Thr759Ala). This variant is present in population databases (rs776873102, gnomAD 0.007%). 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: 288095). 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.

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