Submissions for variant NM_001953.5(TYMP):c.228G>A (p.Met76Ile)

dbSNP: rs1064792859

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Revvity Omics, Revvity	RCV000208657	SCV003827971	uncertain significance	Mitochondrial DNA depletion syndrome 1	2020-01-29	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003479061	SCV004222758	uncertain significance	not specified	2023-11-16	criteria provided, single submitter	clinical testing	Variant summary: TYMP c.228G>A (p.Met76Ile) results in a conservative amino acid change located in the Glycosyl transferase family 3, N-terminal domain (IPR017459) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 249660 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.228G>A has been reported in the literature in individuals affected with Mitochondrial DNA Depletion Syndrome 1 (MNGIE type) (Martin_2004). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 15505189). Two submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. One submitter classified the variant as pathogenic, and one submitter classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance.
GeneReviews	RCV000208657	SCV000264501	pathogenic	Mitochondrial DNA depletion syndrome 1	2016-01-14	no assertion criteria provided	literature only