ClinVar Miner

Submissions for variant NM_002693.3(POLG):c.1349G>T (p.Gly450Val)

gnomAD frequency: 0.00001  dbSNP: rs757804090
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000519409 SCV000620942 uncertain significance not provided 2017-09-22 criteria provided, single submitter clinical testing The G450V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge.This variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The G450V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant isdamaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV000558987 SCV000630092 uncertain significance Progressive sclerosing poliodystrophy 2022-07-05 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 450 of the POLG protein (p.Gly450Val). This variant is present in population databases (rs757804090, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with POLG-related conditions. ClinVar contains an entry for this variant (Variation ID: 452164). 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. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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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