ClinVar Miner

Submissions for variant NM_001363.5(DKC1):c.1058C>T (p.Ala353Val) (rs121912288)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000464438 SCV000553696 pathogenic Dyskeratosis congenita 2019-12-19 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 353 of the DKC1 protein (p.Ala353Val). The alanine residue is highly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (rs121912288, ExAC no frequency). This variant has been reported in numerous individuals affected with dyskeratosis congenita (DKC), and it is known to be the most frequent cause of the disease (PMID: 10364516, 16332973, 19835419). ClinVar contains an entry for this variant (Variation ID: 11587). Experimental studies have shown that this missense change causes defective interaction of the DKC1 protein (known as dyskerin) with human telomerase and leads to impaired telomerase function in vitro and in vivo (PMID: 19835419, 25992652, 22058290, 19391112). For these reasons, this variant has been classified as Pathogenic.
OMIM RCV000012343 SCV000032577 pathogenic Dyskeratosis congenita, X-linked 2009-12-01 no assertion criteria provided literature only
GeneReviews RCV000012343 SCV000055768 pathologic Dyskeratosis congenita, X-linked 2012-05-10 no assertion criteria provided curation Converted during submission to Pathogenic.
UniProtKB/Swiss-Prot RCV000012343 SCV000090817 not provided Dyskeratosis congenita, X-linked no assertion provided not provided

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