ClinVar Miner

Submissions for variant NM_001363.5(DKC1):c.146C>T (p.Thr49Met)

dbSNP: rs121912304
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000254868 SCV000321553 pathogenic not provided 2015-04-27 criteria provided, single submitter clinical testing The T49M variant has been reported previously in a male patient diagnosed with Hoyeraal-Hreidarsson syndrome (Knight et al., 1999). The T49M variant was not observed in approximately 6,500 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 T49M 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 across species. In silico analysis predicts that this substitution is probably damaging to the protein structure/function.
Invitae RCV000816060 SCV000956549 pathogenic Dyskeratosis congenita 2022-04-07 criteria provided, single submitter clinical testing This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects DKC1 function (PMID: 19835419). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C15"). ClinVar contains an entry for this variant (Variation ID: 11591). This missense change has been observed in individuals with dyskeratosis congenita (PMID: 10583221, 11491307, 14648217, 24914498). It has also been observed to segregate with disease in related individuals. This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 49 of the DKC1 protein (p.Thr49Met).
OMIM RCV000012349 SCV000032583 pathogenic Dyskeratosis congenita, X-linked 2009-12-01 no assertion criteria provided literature only
GeneReviews RCV000012349 SCV000055786 not provided Dyskeratosis congenita, X-linked no assertion provided literature only
UniProtKB/Swiss-Prot RCV000012349 SCV000090826 not provided Dyskeratosis congenita, X-linked no assertion provided not provided

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