Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000668721 | SCV000793368 | likely pathogenic | Niemann-Pick disease, type A | 2017-08-24 | criteria provided, single submitter | clinical testing | |
| Ce |
RCV001310952 | SCV001500950 | pathogenic | not provided | 2020-10-01 | criteria provided, single submitter | clinical testing | |
| 3billion | RCV000668721 | SCV002059000 | pathogenic | Niemann-Pick disease, type A | 2022-01-03 | criteria provided, single submitter | clinical testing | Frameshift: predicted to result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant (PVS1_VS). The variant has been reported at least twice as pathogenic/likely pathogenic with clinical assertions and evidence for the classification (ClinVar ID: VCV000553306, PMID:15241805).It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000016, PM2_M). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
| Baylor Genetics | RCV000668721 | SCV004205519 | pathogenic | Niemann-Pick disease, type A | 2023-02-17 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV003767966 | SCV004569718 | pathogenic | Niemann-Pick disease, type B; Niemann-Pick disease, type A | 2023-04-26 | criteria provided, single submitter | clinical testing | This premature translational stop signal has been observed in individual(s) with Niemann-Pick disease (PMID: 33675270). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 553306). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change creates a premature translational stop signal (p.Ala195Serfs*14) in the SMPD1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SMPD1 are known to be pathogenic (PMID: 12369017, 15221801). |