ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.2197C>G (p.Gln733Glu)

gnomAD frequency: 0.00002  dbSNP: rs1471359934
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000695813 SCV000824334 uncertain significance Colorectal cancer, susceptibility to, 10 2024-02-01 criteria provided, single submitter clinical testing This sequence change replaces glutamine, which is neutral and polar, with glutamic acid, which is acidic and polar, at codon 733 of the POLD1 protein (p.Gln733Glu). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 573996). 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 RCV000764226 SCV000895229 uncertain significance Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV002532332 SCV003745373 uncertain significance Inborn genetic diseases 2022-03-29 criteria provided, single submitter clinical testing The c.2197C>G (p.Q733E) alteration is located in exon 18 (coding exon 17) of the POLD1 gene. This alteration results from a C to G substitution at nucleotide position 2197, causing the glutamine (Q) at amino acid position 733 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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