ClinVar Miner

Submissions for variant NM_001256849.1(POLD1):c.883G>A (p.Val295Met) (rs199545019)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236306 SCV000293151 uncertain significance not specified 2017-03-15 criteria provided, single submitter clinical testing This variant is denoted POLD1 c.883G>A at the cDNA level, p.Val295Met (V295M) at the protein level, and results in the change of a Valine to a Methionine (GTG>ATG). Bellido et al. (2015) identified this variant in two kindreds characterized by familial or early-onset mismatch repair proficient colorectal cancer and/or APC and MUTYH-negative polyposes. In one family POLD1 Val295Met was present in both a woman with early-onset colorectal cancer and her mother, who was diagnosed with colorectal cancer at age 70. In the second family, POLD1 Val296Met was observed in trans with a second POLD1 missense variant, Asp316Gly, which the authors interpreted as pathogenic. While the mother in this kindred, who was affected with breast and endometrial cancer, harbored both variants, a daughter affected with both colorectal and endometrial cancer only inherited POLD1 Asp316Gly. POLD1 Val295Met was not observed at a significant allele frequency in the NHLBI Exome Sequencing Project. Since Valine and Methionine share similar properties, this is considered a conservative amino acid substitution. POLD1 Val295Met occurs at a position that is conserved in mammals and is not located in a known functional domain (Tahirov 2009, Preston 2010). In silico analyses are inconsistent regarding the effect this variant may have on protein structure and function. Based on currently available evidence, it is unclear whether POLD1 Val295Met is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
GenomeConnect, ClinGen RCV000509515 SCV000606987 not provided not provided no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.
Invitae RCV000228139 SCV000287655 likely benign Colorectal cancer 10 2018-01-03 criteria provided, single submitter clinical testing
PreventionGenetics RCV000509515 SCV000806567 uncertain significance not provided 2016-10-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000236306 SCV000601960 uncertain significance not specified 2017-06-06 criteria provided, single submitter clinical testing

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