Submissions for variant NM_015046.7(SETX):c.4982C>G (p.Pro1661Arg)

gnomAD frequency: 0.00080  dbSNP: rs146873848

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000558440	SCV000645271	likely benign	Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	2023-12-24	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000558440	SCV000895956	uncertain significance	Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	2018-10-31	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV001644653	SCV001145554	likely benign	not specified	2021-01-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000859806	SCV001822339	uncertain significance	not provided	2022-11-23	criteria provided, single submitter	clinical testing	Reported in single patient from a cohort of individuals with amyotrophic lateral sclerosis; this individual is also reported to harbor a variant in SOD1 (Bartoletti et al., 2021); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33770234)
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV001848953	SCV002105164	uncertain significance	Hereditary spastic paraplegia	2019-12-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002341378	SCV002642204	uncertain significance	Inborn genetic diseases	2020-03-03	criteria provided, single submitter	clinical testing	The p.P1661R variant (also known as c.4982C>G), located in coding exon 8 of the SETX gene, results from a C to G substitution at nucleotide position 4982. The proline at codon 1661 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the supporting evidence, this variant is unlikely to be causative of juvenile amyotrophic lateral sclerosis 4; however, its contribution to the development of spinocerebellar ataxia with axonal neuropathy 2 is uncertain.
Mayo Clinic Laboratories, Mayo Clinic	RCV000859806	SCV004225122	uncertain significance	not provided	2023-06-05	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003925660	SCV004741071	likely benign	SETX-related condition	2022-08-25	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000859806	SCV001806906	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000859806	SCV001927470	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000859806	SCV001964945	likely benign	not provided		no assertion criteria provided	clinical testing