ClinVar Miner

Submissions for variant NM_025099.6(CTC1):c.2192G>A (p.Arg731Gln) (rs201891953)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genetic Services Laboratory,University of Chicago RCV000194118 SCV000247127 uncertain significance not specified 2015-05-04 criteria provided, single submitter clinical testing
Invitae RCV000545908 SCV000631336 uncertain significance Dyskeratosis congenita 2019-12-23 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 731 of the CTC1 protein (p.Arg731Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs201891953, ExAC 0.2%). This variant has not been reported in the literature in individuals with CTC1-related disease. ClinVar contains an entry for this variant (Variation ID: 210794). 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.
Fulgent Genetics,Fulgent Genetics RCV000764154 SCV000895151 uncertain significance Cerebroretinal microangiopathy with calcifications and cysts 1 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000545908 SCV001287773 uncertain significance Dyskeratosis congenita 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.

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