ClinVar Miner

Submissions for variant NM_000400.4(ERCC2):c.1958C>T (p.Thr653Ile)

gnomAD frequency: 0.00001  dbSNP: rs763885481
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Baylor Genetics RCV001788953 SCV002030163 uncertain significance Trichothiodystrophy 1, photosensitive 2021-02-09 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp RCV002034629 SCV002160792 uncertain significance not provided 2022-08-13 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with isoleucine, which is neutral and non-polar, at codon 653 of the ERCC2 protein (p.Thr653Ile). This variant is present in population databases (rs763885481, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ERCC2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1327073). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV002422850 SCV002722084 uncertain significance Inborn genetic diseases 2021-07-05 criteria provided, single submitter clinical testing The p.T653I variant (also known as c.1958C>T), located in coding exon 21 of the ERCC2 gene, results from a C to T substitution at nucleotide position 1958. The threonine at codon 653 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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