Submissions for variant NM_014363.6(SACS):c.1358del (p.Gly453fs)

dbSNP: rs2137722808

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Paris Brain Institute, Inserm - ICM	RCV001391617	SCV001451177	pathogenic	Charlevoix-Saguenay spastic ataxia		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001880216	SCV002185730	pathogenic	Spastic paraplegia	2022-06-13	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 989205). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.Gly453Valfs*25) in the SACS gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in SACS are known to be pathogenic (PMID: 18465152, 20876471).
PROSPAX: an integrated multimodal progression chart in spastic ataxias, Center for Neurology; Hertie-Institute for Clinical Brain Research	RCV001391617	SCV005061986	pathogenic	Charlevoix-Saguenay spastic ataxia	2022-01-01	criteria provided, single submitter	research