Submissions for variant NM_005236.3(ERCC4):c.1391A>T (p.Lys464Ile)

dbSNP: rs780488548

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001300359	SCV001489496	uncertain significance	Xeroderma pigmentosum, group F; Cockayne syndrome; Fanconi anemia complementation group Q	2024-07-26	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with isoleucine, which is neutral and non-polar, at codon 464 of the ERCC4 protein (p.Lys464Ile). This variant is present in population databases (rs780488548, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with ERCC4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1003761). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on ERCC4 protein function. 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.
Laboratory of Molecular Epidemiology of Birth Defects, West China Second University Hospital, Sichuan University	RCV003153976	SCV003843406	benign	Ovarian cancer	2022-01-01	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV005014361	SCV005645252	uncertain significance	Xeroderma pigmentosum, group F; XFE progeroid syndrome; Fanconi anemia complementation group Q	2024-06-04	criteria provided, single submitter	clinical testing