ClinVar Miner

Submissions for variant NM_025099.6(CTC1):c.1459A>G (p.Arg487Gly) (rs747887601)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000428927 SCV000535428 likely pathogenic not provided 2017-01-16 criteria provided, single submitter clinical testing The R487G variant in the CTC1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R487G variant was not observed in approximately 6300 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R487G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. The R487G variant is a strong candidate for a pathogenic variant.
Invitae RCV000634491 SCV000755807 uncertain significance Dyskeratosis congenita 2017-12-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 487 of the CTC1 protein (p.Arg487Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals with CTC1-related disease. ClinVar contains an entry for this variant (Variation ID: 392201). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably 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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