ClinVar Miner

Submissions for variant NM_017646.6(TRIT1):c.967C>T (p.Arg323Trp)

gnomAD frequency: 0.00001  dbSNP: rs370866302
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV002246787 SCV002519899 pathogenic Combined oxidative phosphorylation deficiency 35 2022-05-04 criteria provided, single submitter clinical testing
GeneDx RCV002256943 SCV002526638 pathogenic not provided 2024-07-18 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 31665838, 37471090, 36047296, 35032046)
Labcorp Genetics (formerly Invitae), Labcorp RCV002256943 SCV005697656 likely pathogenic not provided 2025-01-16 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 323 of the TRIT1 protein (p.Arg323Trp). This variant is present in population databases (rs370866302, gnomAD 0.004%). This missense change has been observed in individual(s) with clinical features of TRIT1-related conditions (PMID: 31665838, 35032046, 37471090). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1686274). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt TRIT1 protein function with a positive predictive value of 80%. This variant disrupts the p.Arg323 amino acid residue in TRIT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 24901367, 37393059). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV002246787 SCV004244335 pathogenic Combined oxidative phosphorylation deficiency 35 2024-02-05 no assertion criteria provided literature only

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