ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.575C>T (p.Ala192Val) (rs62621089)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236442 SCV000293761 uncertain significance not specified 2016-01-06 criteria provided, single submitter clinical testing The A192V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project. The A192V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Illumina Clinical Services Laboratory,Illumina RCV000402315 SCV000410259 likely benign Dementia, Deafness, and Sensory Neuropathy 2016-06-14 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757174 SCV000885309 uncertain significance not provided 2018-05-07 criteria provided, single submitter clinical testing The DNMT1 c.575C>T; p.Ala192Val variant (rs62621089, ClinVar variant ID 246280), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with a South Asian population frequency of 0.2% (identified on 67 out of 30,782 chromosomes). The alanine at position 192 is weakly conserved, considering 12 species, and computational analyses of the effects of the p.Ala192Val variant on protein structure and function make conflicting predictions (SIFT: damaging, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Ala192Val variant cannot be determined with certainty.
Invitae RCV000757174 SCV001020732 likely benign not provided 2019-01-29 criteria provided, single submitter clinical testing

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