ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.868G>A (p.Glu290Lys) (rs200024502)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000235414 SCV000293364 uncertain significance not specified 2015-11-21 criteria provided, single submitter clinical testing The E290K 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 E290K variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. However, this substitution occurs at a position outside of the targeting sequence domain that is not conserved, and in silico analysis predicts this variant likely does not alter 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
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000757173 SCV000885308 uncertain significance not provided 2018-02-02 criteria provided, single submitter clinical testing The DNMT1 c.868G>A p.Glu290Lys variant (rs200024502), 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 an overall population frequency of 0.02% (identified on 47 out of 246,268 chromosomes), and is classified as a variant of unknown significance in ClinVar (ID: 246059). The glutamic acid at position 290 is moderately conserved, considering 12 species, and computational analyses of the effects of the p.Glu290Lys variant on protein structure and function do not predict a deleterious effect (SIFT: tolerated, MutationTaster: polymorphism, PolyPhen-2: benign). Based on the available information, the clinical significance of the p.Glu290Lys variant cannot be determined with certainty.
Invitae RCV001082230 SCV001080537 likely benign Hereditary sensory neuropathy type IE 2019-12-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001082230 SCV001282175 benign Hereditary sensory neuropathy type IE 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.

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