Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001210783 | SCV001382288 | likely pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Arg602Valfs*11) in the SMPD1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 30 amino acid(s) of the SMPD1 protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with ASM deficiency (PMID: 27338287; Invitae). ClinVar contains an entry for this variant (Variation ID: 941072). This variant disrupts the C-terminus of the SMPD1 protein. Other variant(s) that disrupt this region (p.Pro606Leufs*7) have been observed in individuals with SMPD1-related conditions (PMID: 27338287). This suggests that this may be a clinically significant region of the protein. 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. |