Submissions for variant NM_014363.6(SACS):c.3144A>G (p.Val1048=)

gnomAD frequency: 0.00035  dbSNP: rs3751369

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000279611	SCV000383363	uncertain significance	Charlevoix-Saguenay spastic ataxia	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Athena Diagnostics	RCV000712974	SCV000843534	benign	not provided	2018-05-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001081930	SCV001004294	benign	Spastic paraplegia	2024-01-31	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000279611	SCV002026659	likely benign	Charlevoix-Saguenay spastic ataxia	2021-09-05	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848104	SCV002105027	likely benign	Hereditary spastic paraplegia	2016-12-12	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000279611	SCV001464171	benign	Charlevoix-Saguenay spastic ataxia	2020-05-02	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004748723	SCV005345087	benign	SACS-related disorder	2024-09-03	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).