ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.1361C>T (p.Ala454Val)

gnomAD frequency: 0.00001  dbSNP: rs1402734026
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000669613 SCV000794384 uncertain significance Niemann-Pick disease, type A 2017-10-07 criteria provided, single submitter clinical testing
Invitae RCV002532089 SCV003439786 uncertain significance Niemann-Pick disease, type B; Niemann-Pick disease, type A 2021-12-08 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 454 of the SMPD1 protein (p.Ala454Val). This variant is present in population databases (no rsID available, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of Niemann-Pick disease (PMID: 12369017). ClinVar contains an entry for this variant (Variation ID: 554055). 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 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.
GeneDx RCV003223664 SCV003919563 likely pathogenic not provided 2022-10-18 criteria provided, single submitter clinical testing Identified in a cohort of patients with Type B Niemann-Pick Disease, although the number of patients harboring this variant (aka A452V) nor clinical details were provided (Simonaro et al., 2002); Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12369017)

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