ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.961C>T (p.His321Tyr)

dbSNP: rs2134012749
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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 RCV001975994 SCV002256553 likely pathogenic Niemann-Pick disease, type B; Niemann-Pick disease, type A 2021-05-21 criteria provided, single submitter clinical testing 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. 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. This variant has been observed in individual(s) with clinical features of Niemann-Pick type A (PMID: 12556236). This variant is not present in population databases (ExAC no frequency). This sequence change replaces histidine with tyrosine at codon 321 of the SMPD1 protein (p.His321Tyr). The histidine residue is highly conserved and there is a moderate physicochemical difference between histidine and tyrosine.

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