Submissions for variant NM_014363.6(SACS):c.10900C>T (p.Gln3634Ter)

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002756833	SCV003022566	pathogenic	Spastic paraplegia	2021-12-03	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SACS protein in which other variant(s) (p.Asn4549Asp) have been determined to be pathogenic (PMID: 15156359, 21507954). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. This variant has not been reported in the literature in individuals affected with SACS-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln3634*) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 946 amino acid(s) of the SACS protein.
Revvity Omics, Revvity	RCV003134495	SCV003814535	likely pathogenic	Charlevoix-Saguenay spastic ataxia	2022-01-11	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003134495	SCV004209984	likely pathogenic	Charlevoix-Saguenay spastic ataxia	2023-05-23	criteria provided, single submitter	clinical testing