NM_017646.6(TRIT1):c.22C>T (p.Arg8Ter) AND not provided

Germline classification:: Pathogenic/Likely pathogenic (2 submissions)
Last evaluated:: May 12, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001796068.7

Allele description [Variation Report for NM_017646.6(TRIT1):c.22C>T (p.Arg8Ter)]

NM_017646.6(TRIT1):c.22C>T (p.Arg8Ter)

Genes:

MYCL-AS1:MYCL antisense RNA 1 [Gene - HGNC]
TRIT1:tRNA isopentenyltransferase 1 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1p34.2

Genomic location:

Preferred name:

NM_017646.6(TRIT1):c.22C>T (p.Arg8Ter)

HGVS:

NC_000001.11:g.39883470G>A
NG_042822.1:g.5042C>T
NM_001312691.1:c.22C>T
NM_001312692.1:c.22C>T
NM_017646.6:c.22C>TMANE SELECT
NP_001299620.1:p.Arg8Ter
NP_001299621.1:p.Arg8Ter
NP_060116.2:p.Arg8Ter
NC_000001.10:g.40349142G>A
NC_000001.10:g.40349142G>A
NM_017646.4:c.22C>T
NM_017646.5:c.22C>T
NR_132401.1:n.42C>T
NR_132402.1:n.42C>T
NR_132403.1:n.42C>T
NR_132404.1:n.42C>T
NR_132405.1:n.42C>T
NR_132406.1:n.42C>T
NR_132407.1:n.42C>T
NR_132408.1:n.42C>T
NR_132409.1:n.42C>T
NR_132410.1:n.42C>T
NR_132412.1:n.42C>T
NR_132413.1:n.42C>T
NR_132414.1:n.42C>T
NR_132415.1:n.42C>T

Protein change:

R8*; ARG8TER

Links:

OMIM: 617840.0006; dbSNP: rs184469579

NCBI 1000 Genomes Browser:

rs184469579

Molecular consequence:

NR_132401.1:n.42C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132402.1:n.42C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132403.1:n.42C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132404.1:n.42C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132405.1:n.42C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132406.1:n.42C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132407.1:n.42C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132408.1:n.42C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132409.1:n.42C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132410.1:n.42C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132412.1:n.42C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132413.1:n.42C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132414.1:n.42C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NR_132415.1:n.42C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_001312691.1:c.22C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001312692.1:c.22C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_017646.6:c.22C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002032685	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Dec 28, 2022)	germline	clinical testing	Citation Link,
SCV002243010	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 12, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 34052969, 24901367, 28185376, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002032685

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Dec 28, 2022)

germline

clinical testing

Citation Link,

SCV002243010

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 12, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic and Clinical Predictors of Ataxia in Pediatric Primary Mitochondrial Disorders.

Martin-Saavedra JS, Teixeira SR, Alves CAPF, Gonçalves FG, Tierradentro-García LO, Kidd M, Muraresku C, Goldstein A, Vossough A.

Cerebellum. 2022 Feb;21(1):116-131. doi: 10.1007/s12311-021-01276-1. Epub 2021 May 30. Erratum in: Cerebellum. 2022 Feb;21(1):132. doi: 10.1007/s12311-022-01370-y.

PubMed [citation]

PMID:: 34052969

Defective i6A37 modification of mitochondrial and cytosolic tRNAs results from pathogenic mutations in TRIT1 and its substrate tRNA.

Yarham JW, Lamichhane TN, Pyle A, Mattijssen S, Baruffini E, Bruni F, Donnini C, Vassilev A, He L, Blakely EL, Griffin H, Santibanez-Koref M, Bindoff LA, Ferrero I, Chinnery PF, McFarland R, Maraia RJ, Taylor RW.

PLoS Genet. 2014 Jun;10(6):e1004424. doi: 10.1371/journal.pgen.1004424.

PubMed [citation]

PMID:: 24901367
PMCID:: PMC4046958

See all PubMed Citations (4)

Details of each submission

From GeneDx, SCV002032685.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Identified in trans with a missense variant, in siblings with neurological disease in published literature (Kernohan et al., 2017); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 28185376, 32948376, 36049610, 36047296, 34052969)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002243010.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 417684). This premature translational stop signal has been observed in individual(s) with clinical features of combined oxidative phosphorylation deficiency (PMID: 28185376, 34052969). This variant is present in population databases (rs184469579, gnomAD 0.06%). This sequence change creates a premature translational stop signal (p.Arg8*) in the TRIT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in TRIT1 are known to be pathogenic (PMID: 24901367, 28185376).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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