Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000534735 | SCV000410263 | likely benign | Hereditary sensory neuropathy-deafness-dementia syndrome | 2017-04-28 | 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
| Labcorp Genetics |
RCV000534735 | SCV000651310 | uncertain significance | Hereditary sensory neuropathy-deafness-dementia syndrome | 2023-12-25 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 137 of the DNMT1 protein (p.Thr137Met). This variant is present in population databases (rs377146699, gnomAD 0.007%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with DNMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 327924). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Eurofins Ntd Llc |
RCV000734145 | SCV000862264 | uncertain significance | not provided | 2018-07-06 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV003352838 | SCV004076042 | uncertain significance | Inborn genetic diseases | 2023-07-26 | criteria provided, single submitter | clinical testing | The c.410C>T (p.T137M) alteration is located in exon 4 (coding exon 4) of the DNMT1 gene. This alteration results from a C to T substitution at nucleotide position 410, causing the threonine (T) at amino acid position 137 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Ce |
RCV000734145 | SCV004139496 | uncertain significance | not provided | 2023-01-01 | criteria provided, single submitter | clinical testing | DNMT1: PP2, BP4 |