Submissions for variant NM_014363.6(SACS):c.5008_5010delinsGTAGATGAATATCTACAATTGTGGATTGTATTTAG (p.Tyr1670fs)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003226801	SCV003923059	likely pathogenic	Charlevoix-Saguenay spastic ataxia	2023-03-27	criteria provided, single submitter	clinical testing	Variant summary: SACS c.5008_5010delins35 (p.Tyr1670ValfsX32) results in a premature termination codon and is predicted to cause a truncation of the encoded protein, which is a commonly known mechanism for disease. Although the variant is not expected to cause absence of the protein through nonsense mediated decay, the variant disrupts more than half of the encoded protein sequence. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 250084 control chromosomes (gnomAD). To our knowledge, no occurrence of c.5008_5010delins35 in individuals affected with Autosomal Recessive Spastic Ataxia Of Charlevoix-Saguenay and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.