Submissions for variant NM_014363.6(SACS):c.8385dup (p.Asp2796fs)

dbSNP: rs2542218493

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002871414	SCV003231975	pathogenic	Spastic paraplegia	2023-01-13	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.Tyr4538*) have been determined to be pathogenic (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 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.Asp2796Argfs*14) in the SACS gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 1784 amino acid(s) of the SACS protein.
Athena Diagnostics	RCV004999820	SCV005621902	likely pathogenic	not provided	2024-06-10	criteria provided, single submitter	clinical testing	This variant has not been reported in large, multi-ethnic general populations. (http://gnomad.broadinstitute.org) This variant is not expected to cause loss of protein expression through nonsense-mediated decay, however, similar variants in this region have been associated with disease, and therefore, this variant is also expected to contribute to disease.