ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.272G>A (p.Cys91Tyr)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV005214849 SCV005858060 likely pathogenic Niemann-Pick disease, type B; Niemann-Pick disease, type A 2024-04-25 criteria provided, single submitter clinical testing This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 91 of the SMPD1 protein (p.Cys91Tyr). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Niemann-Pick disease (Invitae). 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 SMPD1 protein function with a positive predictive value of 95%. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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