Submissions for variant NM_001130823.3(DNMT1):c.3498G>T (p.Gly1166=)

gnomAD frequency: 0.00002  dbSNP: rs1186008456

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000684934	SCV000812397	uncertain significance	Hereditary sensory neuropathy-deafness-dementia syndrome	2018-04-02	criteria provided, single submitter	clinical testing	This sequence change affects codon 1166 of the DNMT1 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the DNMT1 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with DNMT1-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Fulgent Genetics, Fulgent Genetics	RCV002493134	SCV002800843	uncertain significance	Autosomal dominant cerebellar ataxia, deafness and narcolepsy; Hereditary sensory neuropathy-deafness-dementia syndrome	2021-10-21	criteria provided, single submitter	clinical testing