ClinVar Miner

Submissions for variant NM_004287.4(GOSR2):c.509A>G (p.Asn170Ser) (rs150907052)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000187616 SCV000241211 uncertain significance not provided 2017-01-05 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the GOSR2 gene. The N170S variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The N170S variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species, and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, the N170S variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000461893 SCV000543668 uncertain significance Progressive myoclonic epilepsy 2018-11-06 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 170 of the GOSR2 protein (p.Asn170Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs150907052, ExAC 0.03%). This variant has not been reported in the literature in individuals with GOSR2-related disease. ClinVar contains an entry for this variant (Variation ID: 205631). 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. 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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