ClinVar Miner

Submissions for variant NM_001363.5(DKC1):c.361A>G (p.Ser121Gly) (rs121912305)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000479038 SCV000568375 likely pathogenic not provided 2016-11-19 criteria provided, single submitter clinical testing The S121G variant in the DKC1 gene has been reported in two brothers with a diagnosis of Hoyeraal-Hreidarsson syndrome (Knight et al., 2009; Aalfs et al., 1995). The S121G 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 S121G 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 within the protein's catalytic domain that is conserved across species (Vuilliamy et al., 2008). In silico analysis predicts this variant is probably damaging to the protein structure/function. The S121G variant is a strong candidate for a pathogenic variant, however the possibility it may be a rare benign variant cannot be excluded.
OMIM RCV000055630 SCV000032584 pathogenic Dyskeratosis congenita X-linked 2009-12-01 no assertion criteria provided literature only
GeneReviews RCV000012350 SCV000055792 pathologic Hoyeraal Hreidarsson syndrome 2012-05-10 no assertion criteria provided curation Converted during submission to Pathogenic.
UniProtKB/Swiss-Prot RCV000055630 SCV000090832 not provided Dyskeratosis congenita X-linked no assertion provided not provided

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