ClinVar Miner

Submissions for variant NM_017646.6(TRIT1):c.1034A>G (p.Tyr345Cys)

dbSNP: rs2124577339
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV002227864 SCV002507080 uncertain significance Combined oxidative phosphorylation deficiency 35 2022-05-04 criteria provided, single submitter curation The homozygous p.Tyr345Cys variant in TRIT1 was identified by our study in 1 individual with combined oxidative phosphorylation deficiency 35. The variant has been reported in 1 individual of unknown ethnicity with combined oxidative phosphorylation deficiency 35 (PMID: 31140736), but was absent from large population studies. In vitro functional studies provide some evidence that the p.Tyr345Cys variant may slightly impact protein function (PMID: 31140736). However, these types of assays may not accurately represent biological function. Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. The presence of this variant in 1 affected homozygote and in combination with a reported variant of uncertain significance that is confirmed in trans, and in 1 individual with combined oxidative phosphorylation deficiency 35 increases the likelihood that the p.Tyr345Cys variant is pathogenic (PMID: 31140736). In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PM2, PM3_supporting, PS3_supporting (Richards 2015).

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