ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.713C>T (p.Thr238Met)

gnomAD frequency: 0.00007  dbSNP: rs553342844
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236230 SCV000294004 uncertain significance not provided 2021-10-21 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as a pathogenic or benign germline variant to our knowledge; This variant is associated with the following publications: (PMID: 25122428, 9545286, 29056344)
Invitae RCV000475476 SCV000547586 uncertain significance Colorectal cancer, susceptibility to, 10 2024-01-24 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 238 of the POLD1 protein (p.Thr238Met). This variant is present in population databases (rs553342844, gnomAD 0.07%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with POLD1-related conditions. ClinVar contains an entry for this variant (Variation ID: 246444). 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 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.
Fulgent Genetics, Fulgent Genetics RCV000764214 SCV000895217 uncertain significance Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome 2018-10-31 criteria provided, single submitter clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000236230 SCV002010599 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing

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