ClinVar Miner

Submissions for variant NM_015046.7(SETX):c.1343A>G (p.Asp448Gly) (rs370363342)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000695198 SCV000823683 uncertain significance Amyotrophic lateral sclerosis type 4; Spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 2019-09-05 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 448 of the SETX protein (p.Asp448Gly). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs370363342, ExAC 0.1%). This variant has been observed in an individual affected with amyotrophic lateral sclerosis (PMID: 30220148). ClinVar contains an entry for this variant (Variation ID: 573505). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Athena Diagnostics Inc RCV000992929 SCV001145533 likely benign not provided 2019-04-10 criteria provided, single submitter clinical testing

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