ClinVar Miner

Submissions for variant NM_000543.5(SMPD1):c.551C>T (p.Pro184Leu)

gnomAD frequency: 0.00006  dbSNP: rs760203204
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000596004 SCV000709368 uncertain significance not provided 2017-06-23 criteria provided, single submitter clinical testing
Invitae RCV001037515 SCV001200931 pathogenic Niemann-Pick disease, type B; Niemann-Pick disease, type A 2023-10-17 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 184 of the SMPD1 protein (p.Pro184Leu). This variant is present in population databases (rs760203204, gnomAD 0.03%). This missense change has been observed in individuals with SMPD1-related conditions (PMID: 16642440, 17011332). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 502573). 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. Experimental studies have shown that this missense change affects SMPD1 function (PMID: 16642440). For these reasons, this variant has been classified as Pathogenic.

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