ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.742G>C (p.Glu248Gln)

dbSNP: rs200763423
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV002037625 SCV002234875 pathogenic Niemann-Pick disease, type B; Niemann-Pick disease, type A 2023-03-08 criteria provided, single submitter clinical testing This variant is present in population databases (no rsID available, gnomAD 0.0009%). For these reasons, this variant has been classified as Pathogenic. This variant disrupts the p.Glu248 amino acid residue in SMPD1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 15221801, 19411774). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Experimental studies have shown that this missense change affects SMPD1 function (PMID: 8664904). 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. ClinVar contains an entry for this variant (Variation ID: 1452305). This missense change has been observed in individual(s) with Niemann-Pick disease type B (PMID: 8664904). This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 248 of the SMPD1 protein (p.Glu248Gln).

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