Submissions for variant NM_015046.7(SETX):c.1427_1432del (p.His476_Leu477del)

dbSNP: rs777314512

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Athena Diagnostics Inc	RCV001560100	SCV000615158	uncertain significance	not provided	2023-01-27	criteria provided, single submitter	clinical testing	Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools yielded predictions that this variant is unlikely to have an effect on normal RNA splicing.
Invitae	RCV001229711	SCV001402165	uncertain significance	Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	2019-07-19	criteria provided, single submitter	clinical testing	This variant, c.1427_1432del, results in the deletion of 2 amino acid(s) of the SETX protein (p.His476_Leu477del), but otherwise preserves the integrity of the reading frame. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated for this variant, and the functional significance of the affected amino acid(s) is currently unknown. This variant has not been reported in the literature in individuals with SETX-related conditions. This variant is present in population databases (rs777314512, ExAC 0.005%).
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001560100	SCV001471402	uncertain significance	not provided	2020-04-24	criteria provided, single submitter	clinical testing	The SETX c.1427_1432del; p.His476_Leu477del variant (rs777314512), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 448305). This variant is found in the population with an overall allele frequency of 0.001 % (4/ 272,150 alleles) in the Genome Aggregation Database. This variant deletes a two residue leaving the rest of the protein in-frame. Due to limited information, the clinical significance of the p.His476_Leu477del variant is uncertain at this time.
GeneDx	RCV001560100	SCV001782440	uncertain significance	not provided	2019-07-30	criteria provided, single submitter	clinical testing	In-frame deletion of 2 amino acids in a non-repeat region; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002395237	SCV002698444	uncertain significance	Inborn genetic diseases	2020-03-20	criteria provided, single submitter	clinical testing	The c.1427_1432delATTTGC variant (also known as p.H476_L477del) is located in coding exon 8 of the SETX gene. This variant results from an in-frame deletion of 6 nucleotides from positions 1427 to 1432. This results in the in-frame deletion of histidine and leucine residues at codons 476 and 477, respectively. These amino acid positions are well conserved in available vertebrate species. In addition, this variant is predicted to be deleterious by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Genome-Nilou Lab	RCV003233665	SCV003931552	uncertain significance	Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2	2023-02-08	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV003233666	SCV003931553	uncertain significance	Amyotrophic lateral sclerosis type 4	2023-02-08	criteria provided, single submitter	clinical testing