Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Research Center, |
RCV000504182 | SCV000588361 | uncertain significance | Niemann-Pick disease, type A | 2020-05-03 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000504182 | SCV000794352 | uncertain significance | Niemann-Pick disease, type A | 2017-10-08 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV002524354 | SCV003439609 | likely pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2022-03-03 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. 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: 437453). This variant is also known as p.Y517C. This missense change has been observed in individuals with Niemann-Pick disease type A (PMID: 15221801, 27338287). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 519 of the SMPD1 protein (p.Tyr519Cys). |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689767 | SCV005185752 | uncertain significance | not specified | 2024-05-15 | criteria provided, single submitter | clinical testing | Variant summary: SMPD1 c.1556A>G (p.Tyr519Cys; also described as c.1550A>G; p.Y517C in the literature) results in a non-conservative amino acid change located in the sphingomyelin phosphodiesterase, C-terminal domain (IPR045473) of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251342 control chromosomes (gnomAD). c.1556A>G has been reported in the literature in individuals affected with Niemann-Pick Disease (Ricci_2004, Ranganath_2016). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 27338287, 15221801). ClinVar contains an entry for this variant (Variation ID: 437453). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |