Submissions for variant NC_012920.1(MT-TW):m.5558A>G

dbSNP: rs370471013

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen	RCV001796795	SCV002037602	uncertain significance	Mitochondrial disease	2021-12-10	reviewed by expert panel	curation	The m.5558A>G variant in MT-TW was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel as part of the variant pilot for mitochondrial DNA variant specifications (McCormick et al., 2020; PMID: 32906214). There have been no affected individuals reported in the medical literature to our knowledge. There are no large families reported in the medical literature to consider for evidence of segregation. There are over 100 occurrences in MITOMAP for an overall allele frequency of 0.2%. This does not meet criteria for BA1 or BS1. The computational predictor MitoTIP suggests this variant is possibly benign (31st percentile) and HmtVAR predicts it to be likely polymorphic (0.5, BP4). There are no cybrid or single fiber studies reported on this variant. In summary, this variant meets criteria to be classified as uncertain significance for primary mitochondrial disease inherited in a mitochondrial manner. This classification was approved by the NICHD U24 Mitochondrial Disease Variant Curation Expert Panel as of August 20, 2020. Mitochondrial DNA-specific ACMG/AMP criteria applied: BP4.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000850795	SCV000993028	benign	MELAS syndrome	2019-07-12	criteria provided, single submitter	clinical testing	The NC_012920.1:m.5558A>G variant in MT-TW gene is interpreted to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS1, BS2, BP4, BP5