Submissions for variant NM_014363.6(SACS):c.7162_7163del (p.Thr2388fs)

dbSNP: rs1555251539

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics Inc	RCV000516377	SCV000614975	likely pathogenic	not provided	2016-12-09	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000516377	SCV001447034	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001785652	SCV002027643	likely pathogenic	Charlevoix-Saguenay spastic ataxia	2021-09-05	criteria provided, single submitter	clinical testing
Invitae	RCV001857925	SCV002228684	pathogenic	Spastic paraplegia	2023-03-24	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 448217). 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.Tyr4538*) have been determined to be pathogenic (PMID: 15156359, 21507954; Invitae). 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 premature translational stop signal has been observed in individual(s) with hereditary spastic paraplegia (PMID: 29538656). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Thr2388Argfs*10) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 2192 amino acid(s) of the SACS protein.
Baylor Genetics	RCV001785652	SCV004209888	pathogenic	Charlevoix-Saguenay spastic ataxia	2023-10-14	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001785652	SCV002086227	likely pathogenic	Charlevoix-Saguenay spastic ataxia	2020-07-09	no assertion criteria provided	clinical testing