Submissions for variant NM_014363.6(SACS):c.2602A>G (p.Ile868Val)

gnomAD frequency: 0.00040  dbSNP: rs142284018

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics Inc	RCV000518481	SCV000614946	uncertain significance	not provided	2018-07-23	criteria provided, single submitter	clinical testing
Invitae	RCV000820462	SCV000961177	likely benign	Spastic paraplegia	2024-01-21	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001111916	SCV001269523	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.
GeneDx	RCV000518481	SCV001993018	uncertain significance	not provided	2019-06-28	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genome-Nilou Lab	RCV001111916	SCV002026668	uncertain significance	Charlevoix-Saguenay spastic ataxia	2021-09-05	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848891	SCV002105019	uncertain significance	Hereditary spastic paraplegia	2016-12-12	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002525072	SCV003687442	uncertain significance	Inborn genetic diseases	2022-02-09	criteria provided, single submitter	clinical testing	The c.2602A>G (p.I868V) alteration is located in exon 10 (coding exon 9) of the SACS gene. This alteration results from a A to G substitution at nucleotide position 2602, causing the isoleucine (I) at amino acid position 868 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.