Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ce |
RCV001092943 | SCV001249691 | pathogenic | not provided | 2017-08-01 | criteria provided, single submitter | clinical testing | |
Molecular Medicine for Neurodegenerative and Neuromuscular Diseases Unit, |
RCV000043632 | SCV001519129 | pathogenic | Autosomal dominant cerebellar ataxia, deafness and narcolepsy | 2021-01-04 | criteria provided, single submitter | research | |
Gene |
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, |
RCV002513639 | SCV004174786 | uncertain significance | Hereditary sensory neuropathy-deafness-dementia syndrome | 2016-01-06 | no assertion criteria provided | literature only |