ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.1840C>T (p.His614Tyr)

gnomAD frequency: 0.00001  dbSNP: rs144277999
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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 RCV001223018 SCV001395147 uncertain significance Colorectal cancer, susceptibility to, 10 2023-06-18 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. 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) performed at Invitae indicates that this missense variant is not expected to disrupt POLD1 protein function. ClinVar contains an entry for this variant (Variation ID: 951165). This variant has not been reported in the literature in individuals affected with POLD1-related conditions. This variant is present in population databases (rs144277999, gnomAD 0.007%). This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 614 of the POLD1 protein (p.His614Tyr).
Ambry Genetics RCV002411823 SCV002716387 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-16 criteria provided, single submitter clinical testing The p.H614Y variant (also known as c.1840C>T), located in coding exon 14 of the POLD1 gene, results from a C to T substitution at nucleotide position 1840. The histidine at codon 614 is replaced by tyrosine, an amino acid with similar properties. This amino acid position is conserved. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics RCV005021531 SCV005650302 uncertain significance Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome; Immunodeficiency 120 2024-04-21 criteria provided, single submitter clinical testing

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