ClinVar Miner

Submissions for variant NM_018006.5(TRMU):c.835G>A (p.Val279Met) (rs387907022)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000442392 SCV000520994 likely pathogenic not provided 2016-10-31 criteria provided, single submitter clinical testing The V279M variant in the TRMU gene has been previously reported in the compound heterozygous state in an individual with acute liver failure in infancy, as well as an individual with infantile reversible cytochrome c oxidase deficiency (Zeharia et al., 2009; Uusimaa et al., 2011). The V279M variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The V279M variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded.
Ambry Genetics RCV000623265 SCV000741012 pathogenic Inborn genetic diseases 2015-09-22 criteria provided, single submitter clinical testing
Counsyl RCV000023804 SCV000793233 likely pathogenic Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins 2017-08-07 criteria provided, single submitter clinical testing
Invitae RCV000442392 SCV000961895 likely pathogenic not provided 2019-11-29 criteria provided, single submitter clinical testing This sequence change replaces valine with methionine at codon 279 of the TRMU protein (p.Val279Met). The valine residue is highly conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs387907022, ExAC 0.04%). This variant has been reported in the compound-heterozygous state in several individuals affected with acute infantile liver failure or infantile reversible respiratory chain deficiency (PMID: 21931168, 19732863, 25665837, 23625533). ClinVar contains an entry for this variant (Variation ID: 30819). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Centogene AG - the Rare Disease Company RCV000023804 SCV001424508 pathogenic Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins criteria provided, single submitter clinical testing
OMIM RCV000023804 SCV000045095 pathogenic Acute infantile liver failure due to synthesis defect of mtDNA-encoded proteins 2011-10-01 no assertion criteria provided literature only

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