ClinVar Miner

Submissions for variant NM_000271.5(NPC1):c.2224G>A (p.Glu742Lys)

dbSNP: rs1555634202
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000673722 SCV000798957 uncertain significance Niemann-Pick disease, type C1 2018-04-04 criteria provided, single submitter clinical testing
Invitae RCV000673722 SCV003443334 uncertain significance Niemann-Pick disease, type C1 2022-03-29 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 742 of the NPC1 protein (p.Glu742Lys). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with clinical features of Niemann-Pick disease type C (PMID: 12955717, 33258288). ClinVar contains an entry for this variant (Variation ID: 557565). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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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