Submissions for variant NM_015046.7(SETX):c.6313C>T (p.Arg2105Trp)

gnomAD frequency: 0.00001  dbSNP: rs142843968

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000342521	SCV000477806	uncertain significance	Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	2018-01-12	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.
Illumina Laboratory Services, Illumina	RCV000407208	SCV000477807	uncertain significance	Amyotrophic lateral sclerosis type 4	2018-01-12	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.
Invitae	RCV001358835	SCV001554687	benign	Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	2023-11-01	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV001662351	SCV001880519	uncertain significance	not provided	2020-12-08	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002365439	SCV002656766	uncertain significance	Inborn genetic diseases	2020-07-23	criteria provided, single submitter	clinical testing	The p.R2105W variant (also known as c.6313C>T), located in coding exon 15 of the SETX gene, results from a C to T substitution at nucleotide position 6313. The arginine at codon 2105 is replaced by tryptophan, an amino acid with dissimilar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx	RCV001662351	SCV004030940	uncertain significance	not provided	2023-02-24	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 28539123)
CeGaT Center for Human Genetics Tuebingen	RCV001662351	SCV004702787	uncertain significance	not provided	2024-01-01	criteria provided, single submitter	clinical testing	SETX: PM2:Supporting