Submissions for variant NM_000543.5(SMPD1):c.1666C>T (p.His556Tyr)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003781119	SCV004570148	uncertain significance	Niemann-Pick disease, type B; Niemann-Pick disease, type A	2023-01-13	criteria provided, single submitter	clinical testing	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. 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on SMPD1 protein function. This missense change has been observed in individual(s) with Niemann-Pick disease type B (PMID: 22367733). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs780415152, gnomAD 0.007%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 556 of the SMPD1 protein (p.His556Tyr).