ClinVar Miner

Submissions for variant NM_005236.2(ERCC4):c.1765C>T (p.Arg589Trp) (rs147105770)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Fulgent Genetics,Fulgent Genetics RCV000762956 SCV000893393 pathogenic Xeroderma pigmentosum, group F; XFE progeroid syndrome; Fanconi anemia, complementation group Q 2018-10-31 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000049250 SCV000594580 likely pathogenic Xeroderma pigmentosum, type f/Cockayne syndrome 2017-01-19 criteria provided, single submitter clinical testing
Invitae RCV000700109 SCV000828850 likely pathogenic Xeroderma pigmentosum, group F; Cockayne syndrome; Fanconi anemia, complementation group Q 2017-09-12 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 589 of the ERCC4 protein (p.Arg589Trp). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs147105770, ExAC 0.02%). This variant has been observed  in multiple individuals with xeroderma pigmentosa (PMID: 20221251, 23623389, 21612988, 26074087, 26884178), and is on the opposite chromosome (in trans) of a pathogenic variant in at least one of these individuals (PMID: 20221251) This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 55829). Experimental studies have shown that this missense change (p.Arg589Trp) leads to protein instability and disrupts binding between the ERCC4 and SLX4 proteins (PMID: 26453996). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000049250 SCV000077503 pathogenic Xeroderma pigmentosum, type f/Cockayne syndrome 2013-05-02 no assertion criteria provided literature only

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