ClinVar Miner

Submissions for variant NM_015046.7(SETX):c.5051C>G (p.Ser1684Cys) (rs140116005)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757760 SCV000886105 uncertain significance not provided 2018-01-12 criteria provided, single submitter clinical testing The SETX c.5051C>G p.Ser1684Cys variant (rs140116005), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.01 % (identified on 38 out of 277,110 chromosomes). The serine at position 1684 is weakly conserved, considering 12 species, and computational analyses of the effects of the p.Ser1684Cys variant on protein structure and function do not agree (SIFT: damaging, MutationTaster: polymorphism, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Ser1684Cys variant cannot be determined with certainty.
Athena Diagnostics Inc RCV000757760 SCV001145555 uncertain significance not provided 2018-09-07 criteria provided, single submitter clinical testing
Invitae RCV001047649 SCV001211619 uncertain significance Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2019-09-16 criteria provided, single submitter clinical testing This sequence change replaces serine with cysteine at codon 1684 of the SETX protein (p.Ser1684Cys). The serine residue is weakly conserved and there is a moderate physicochemical difference between serine and cysteine. This variant is present in population databases (rs140116005, ExAC 0.02%). This variant has not been reported in the literature in individuals with SETX-related conditions. ClinVar contains an entry for this variant (Variation ID: 618872). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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