ClinVar Miner

Submissions for variant NM_002691.4(POLD1):c.3298G>A (p.Gly1100Arg)

dbSNP: rs1060501837
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000456639 SCV000547615 uncertain significance Colorectal cancer, susceptibility to, 10 2023-08-22 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. Experimental studies have shown that this missense change affects POLD1 function (PMID: 31944473). 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: 408063). This missense change has been observed in individual(s) with autosomal recessive non-syndromic sensorineural hearing loss (PMID: 31944473). It has also been observed to segregate with disease in related individuals. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 1100 of the POLD1 protein (p.Gly1100Arg).
Fulgent Genetics, Fulgent Genetics RCV000764233 SCV000895236 uncertain significance Colorectal cancer, susceptibility to, 10; Mandibular hypoplasia-deafness-progeroid syndrome 2018-10-31 criteria provided, single submitter clinical testing
GeneDx RCV001753885 SCV001985871 uncertain significance not provided 2021-04-15 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); Identified in trans with a POLD1 loss of function variant in two siblings with nonsyndromic sensorineural hearing loss (Oh 2020); Published functional studies demonstrate reduced DNA polymerization activity in vitro, but protein stability comparable to wild-type (Oh 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31944473)

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