Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Eurofins Ntd Llc |
RCV000593641 | SCV000700829 | likely pathogenic | not provided | 2017-02-21 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV003465330 | SCV004209880 | likely pathogenic | Charlevoix-Saguenay spastic ataxia | 2023-10-26 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004782459 | SCV005395278 | uncertain significance | not specified | 2024-09-20 | criteria provided, single submitter | clinical testing | Variant summary: SACS c.13615C>T (p.Pro4539Ser) results in a non-conservative amino acid change located in the HEPN functional domain (PMID: 24030952) of the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 251420 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.13615C>T has been reported in the literature in at least three compound heterozygous individuals affected with Autosomal Recessive Spastic Ataxia Of Charlevoix-Saguenay (e.g., Nemeth_2015, Truong_2022, Retterer_2016), and the variant was shown to segregate with disease in one family (e.g., Truong_2022). 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: 24030952, 36600740, 26633542). ClinVar contains an entry for this variant (Variation ID: 496951). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |