Submissions for variant NM_001983.4(ERCC1):c.793G>A (p.Ala265Thr)

gnomAD frequency: 0.00045  dbSNP: rs144868115

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001752757	SCV001997706	uncertain significance	not provided	2022-02-07	criteria provided, single submitter	clinical testing	In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 24158589)
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden	RCV001752757	SCV002010496	uncertain significance	not provided	2021-11-03	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001752757	SCV003262625	uncertain significance	not provided	2022-07-03	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The threonine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 265 of the ERCC1 protein (p.Ala265Thr). This variant is present in population databases (rs144868115, gnomAD 0.1%). This variant has not been reported in the literature in individuals affected with ERCC1-related conditions. ClinVar contains an entry for this variant (Variation ID: 1311774).