ClinVar Miner

Submissions for variant NM_001130823.3(DNMT1):c.1709C>T (p.Ala570Val)

dbSNP: rs397509392
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001092943 SCV001249691 pathogenic not provided 2017-08-01 criteria provided, single submitter clinical testing
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, IRCCS Fondazione Stella Maris RCV000043632 SCV001519129 pathogenic Autosomal dominant cerebellar ataxia, deafness and narcolepsy 2021-01-04 criteria provided, single submitter research
GeneDx RCV001092943 SCV002061015 pathogenic not provided 2022-09-13 criteria provided, single submitter clinical testing Published functional studies demonstrate a damaging effect resulting in aberrant protein localization and reduced cellular ATP levels (Mishima et al., 2020); Not observed at significant frequency in large population cohorts (gnomAD); 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: 24727570, 24709307, 27602171, 27869457, 32754641, 31984424, 31680384, 25678562, 23521649, 25942534, 22328086)
Invitae RCV002513639 SCV003442656 pathogenic Hereditary sensory neuropathy-deafness-dementia syndrome 2022-03-14 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Experimental studies have shown that this missense change affects DNMT1 function (PMID: 31984424). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 50920). This missense change has been observed in individual(s) with cerebellar ataxia, deafness, and narcolepsy (PMID: 22328086). In at least one individual the variant was observed to be de novo. 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 alanine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 570 of the DNMT1 protein (p.Ala570Val).
OMIM RCV000043632 SCV000071657 pathogenic Autosomal dominant cerebellar ataxia, deafness and narcolepsy 2012-05-15 no assertion criteria provided literature only
Inherited Neuropathy Consortium Ii, University Of Miami RCV002513639 SCV004174786 uncertain significance Hereditary sensory neuropathy-deafness-dementia syndrome 2016-01-06 no assertion criteria provided literature only

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