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NM_018006.5(TRMU):c.680G>C (p.Arg227Thr) AND not provided

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Sep 8, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV001879773.4

Allele description [Variation Report for NM_018006.5(TRMU):c.680G>C (p.Arg227Thr)]

NM_018006.5(TRMU):c.680G>C (p.Arg227Thr)

Gene:
TRMU:tRNA mitochondrial 2-thiouridylase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
22q13.31
Genomic location:
Preferred name:
NM_018006.5(TRMU):c.680G>C (p.Arg227Thr)
HGVS:
  • NC_000022.11:g.46352149G>C
  • NG_012173.1:g.21749G>C
  • NM_001282782.2:c.338G>C
  • NM_001282783.2:c.260G>C
  • NM_001282784.2:c.260G>C
  • NM_001282785.2:c.680G>C
  • NM_018006.5:c.680G>CMANE SELECT
  • NP_001269711.1:p.Arg113Thr
  • NP_001269712.1:p.Arg87Thr
  • NP_001269713.1:p.Arg87Thr
  • NP_001269714.1:p.Arg227Thr
  • NP_060476.2:p.Arg227Thr
  • NC_000022.10:g.46748046G>C
  • NC_000022.10:g.46748046G>C
  • NM_018006.3:c.680G>C
  • NM_018006.4:c.680G>C
  • NR_104240.2:n.676G>C
  • NR_104241.2:n.569G>C
Protein change:
R113T
Links:
dbSNP: rs764622793
NCBI 1000 Genomes Browser:
rs764622793
Molecular consequence:
  • NM_001282782.2:c.338G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282783.2:c.260G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282784.2:c.260G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001282785.2:c.680G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_018006.5:c.680G>C - missense variant - [Sequence Ontology: SO:0001583]
  • NR_104240.2:n.676G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NR_104241.2:n.569G>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002246212Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Likely pathogenic
(Sep 8, 2023)
germlineclinical testing

PubMed (4)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Use of Exome Sequencing for Infants in Intensive Care Units: Ascertainment of Severe Single-Gene Disorders and Effect on Medical Management.

Meng L, Pammi M, Saronwala A, Magoulas P, Ghazi AR, Vetrini F, Zhang J, He W, Dharmadhikari AV, Qu C, Ward P, Braxton A, Narayanan S, Ge X, Tokita MJ, Santiago-Sim T, Dai H, Chiang T, Smith H, Azamian MS, Robak L, Bostwick BL, et al.

JAMA Pediatr. 2017 Dec 4;171(12):e173438. doi: 10.1001/jamapediatrics.2017.3438. Epub 2017 Dec 4.

PubMed [citation]
PMID:
28973083
PMCID:
PMC6359927

L-Cysteine supplementation prevents liver transplantation in a patient with TRMU deficiency.

Soler-Alfonso C, Pillai N, Cooney E, Mysore KR, Boyer S, Scaglia F.

Mol Genet Metab Rep. 2019 Jun;19:100453. doi: 10.1016/j.ymgmr.2019.100453.

PubMed [citation]
PMID:
30740308
PMCID:
PMC6355510
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002246212.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

This sequence change replaces arginine, which is basic and polar, with threonine, which is neutral and polar, at codon 227 of the TRMU protein (p.Arg227Thr). This variant is present in population databases (rs764622793, gnomAD 0.01%). This missense change has been observed in individual(s) with transient infantile liver failure (PMID: 28973083, 30740308, 33365252). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 973463). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt TRMU protein function. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024