Submissions for variant NM_001130823.3(DNMT1):c.4414C>T (p.Arg1472Trp)

dbSNP: rs2089501636

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001244852	SCV001418102	uncertain significance	Hereditary sensory neuropathy-deafness-dementia syndrome	2021-12-02	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 1472 of the DNMT1 protein (p.Arg1472Trp). This variant is not present in population databases (gnomAD no frequency). 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: 969489). 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"). 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.
CeGaT Center for Human Genetics Tuebingen	RCV003426012	SCV004146638	uncertain significance	not provided	2022-03-01	criteria provided, single submitter	clinical testing	DNMT1: PM2, PP2