Submissions for variant NC_012920.1(MT-TS1):m.7502C>T

dbSNP: rs876657868

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
ClinGen Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel, ClinGen	RCV003319188	SCV004023284	uncertain significance	Mitochondrial disease	2023-07-24	reviewed by expert panel	curation	The m.7502C>T variant in MT-TS1 was reviewed by the Mitochondrial Disease Nuclear and Mitochondrial Variant Curation Expert Panel on July 24, 2023. There are no individuals or families with primary mitochondrial disease with this variant reported in the medical literature to our knowledge. This variant has been reported in one individual in the medical literature, in an individual of Han Chinese descent with a tic disorder (PMID: 33289513). Other features were not reported and other genetic etiologies were not assessed. There are several occurrences in population databases. This variant is present in 0.007% of individuals in GenBank MITOMAP sequences, in 0.009% of individuals in gnomAD v3.1.2 (homoplasmic in all five individuals), and in 0.004% of individuals in the Helix dataset (six homoplasmic occurrences, one heteroplasmic). MitoTIP suggests this variant is benign (8.2 percentile) and HmtVAR predicts it to be polymorphic (0.1; BP4). There are no cybrid, single fiber, or other studies reported for 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/NINDS U24 ClinGen Mitochondrial Disease Variant Curation Expert Panel on July 24, 2023. Mitochondrial DNA-specific ACMG/AMP criteria applied (PMID: 32906214): BP4.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000218791	SCV000271982	uncertain significance	not specified	2016-04-07	criteria provided, single submitter	clinical testing	The m.7502C>T variant in MT-TS1 has not been previously reported in individuals with hearing loss. This variant has been identified in 3/30589 human mitochondri al DNA sequences of various ancestries (http://www.mitomap.org). In summary, the clinical significance of the m.7502C>T variant is uncertain.
Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine	RCV000850905	SCV000993139	likely benign	MELAS syndrome	2019-07-12	criteria provided, single submitter	clinical testing	The NC_012920.1:m.7502C>T variant in MT-TS1 gene is interpreted to be a Likely Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes reported in the guidelines: BS2, BP4, BP6