ClinVar Miner

Submissions for variant NM_006231.4(POLE):c.314A>G (p.Tyr105Cys)

gnomAD frequency: 0.00009  dbSNP: rs1451750169
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV003656753 SCV001415002 uncertain significance not provided 2024-08-29 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 105 of the POLE protein (p.Tyr105Cys). This variant is present in population databases (no rsID available, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with POLE-related conditions. ClinVar contains an entry for this variant (Variation ID: 967117). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt POLE protein function with a negative predictive value of 80%. 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 RCV003166508 SCV003897109 uncertain significance Hereditary cancer-predisposing syndrome 2022-12-18 criteria provided, single submitter clinical testing The p.Y105C variant (also known as c.314A>G), located in coding exon 4 of the POLE gene, results from an A to G substitution at nucleotide position 314. The tyrosine at codon 105 is replaced by cysteine, an amino acid with highly dissimilar 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.
Fulgent Genetics, Fulgent Genetics RCV005005113 SCV005633776 uncertain significance Colorectal cancer, susceptibility to, 12; Facial dysmorphism-immunodeficiency-livedo-short stature syndrome; Intrauterine growth retardation, metaphyseal dysplasia, adrenal hypoplasia congenita, genital anomalies, and immunodeficiency 2024-02-15 criteria provided, single submitter clinical testing

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