ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.416T>C (p.Leu139Pro)

dbSNP: rs797044797
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV001169955 SCV001251790 likely pathogenic not provided 2020-05-03 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001582677 SCV001821687 likely pathogenic Niemann-Pick disease, type B 2021-07-22 criteria provided, single submitter clinical testing
Invitae RCV003765159 SCV004570128 pathogenic Niemann-Pick disease, type B; Niemann-Pick disease, type A 2023-11-24 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 139 of the SMPD1 protein (p.Leu139Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with Niemann-Pick disease type B (PMID: 12369017, 34554397). This variant is also known as L137P. ClinVar contains an entry for this variant (Variation ID: 203424). 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%. For these reasons, this variant has been classified as Pathogenic.
GeneReviews RCV000192219 SCV000238486 not provided Sphingomyelin/cholesterol lipidosis no assertion provided literature only Some evidence suggests that this pathogenic variant is associated with a less severe form of Niemann-Pick disease type B

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