Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000236861 | SCV000294108 | pathogenic | not provided | 2023-09-29 | criteria provided, single submitter | clinical testing | Published functional studies suggest an impact on splicing and a damaging effect on protein function (Johnson et al., 2021; Mohassel et al., 2021; Kolbel et al., 2022 Lone et al., 2022); Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 34459874, 34059824, 35627278, 35900868) |
Victorian Clinical Genetics Services, |
RCV004594033 | SCV005086412 | pathogenic | Neuropathy, hereditary sensory and autonomic, type 1A | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as pathogenic. Following criteria are met: 0105 - The mechanism of disease for this gene is not clearly established. (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0210 - Splice site variant proven to affect splicing of the transcript with a known effect on protein sequence. This missense variant results in complete skipping of exon 2 of the SPTLC1 protein (PMID: 34059824). (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0604 - Variant is not located in an established domain, motif, hotspot or informative constraint region. (I) 0705 - No comparable variants have previous evidence for pathogenicity. (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. This variant has been reported as de novo in three individuals with juvenile amyotrophic lateral sclerosis (Johnson, JO. et al. (2020) PriPrint, PMID: 34059824). It has also been reported as VUS once in ClinVar. (SP) 0905 - No published segregation evidence has been identified for this variant. (I) 1002 - This variant has moderate functional evidence supporting abnormal protein function. Functional data demonstrated abnormal SPTLC1 function by measuring sphingolipids extracted from plasma (Johnson, JO. et al. (2020) PriPrint). (SP) 1102 - Strong phenotype match for this individual. (SP) 1204 - This variant has been shown to be de novo in the proband (parental status not tested but assumed). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |
OMIM | RCV003223342 | SCV003841242 | pathogenic | Amyotrophic lateral sclerosis 27, juvenile | 2023-03-14 | no assertion criteria provided | literature only |