Submissions for variant NM_014363.6(SACS):c.13176C>G (p.Tyr4392Ter)

dbSNP: rs1285760809

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002568880	SCV003482059	pathogenic	Spastic paraplegia	2022-09-07	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. ClinVar contains an entry for this variant (Variation ID: 1175062). 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.Tyr4392*) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 188 amino acid(s) of the SACS protein.
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research	RCV004764969	SCV005044587	pathogenic	Charlevoix-Saguenay spastic ataxia	2022-01-01	criteria provided, single submitter	research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529804	SCV001743902	pathogenic	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001529804	SCV001957703	pathogenic	not provided		no assertion criteria provided	clinical testing