NM_017646.6(TRIT1):c.22C>T (p.Arg8Ter) AND Combined oxidative phosphorylation deficiency 35

Germline classification:: Pathogenic/Likely pathogenic (3 submissions)
Last evaluated:: Dec 8, 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:: RCV000584740.2

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)

Name:: Combined oxidative phosphorylation deficiency 35 (COXPD35)
Identifiers:: MONDO: MONDO:0054742; MedGen: C4693466; OMIM: 617873

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000692463	OMIM	no assertion criteria provided	Pathogenic (Feb 16, 2018)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000883202	SIB Swiss Institute of Bioinformatics	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Oct 15, 2018)	unknown	curation	PubMed (2) [See all records that cite these PMIDs] 28185376, 25741868
SCV005049810	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Dec 8, 2023)	unknown	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000692463

OMIM

no assertion criteria provided

Pathogenic
(Feb 16, 2018)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV000883202

SIB Swiss Institute of Bioinformatics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Oct 15, 2018)

unknown

curation

PubMed (2)
[See all records that cite these PMIDs]

SCV005049810

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Dec 8, 2023)

unknown

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing, curation

Citations

PubMed

Matchmaking facilitates the diagnosis of an autosomal-recessive mitochondrial disease caused by biallelic mutation of the tRNA isopentenyltransferase (TRIT1) gene.

Kernohan KD, Dyment DA, Pupavac M, Cramer Z, McBride A, Bernard G, Straub I, Tetreault M, Hartley T, Huang L, Sell E, Majewski J, Rosenblatt DS, Shoubridge E, Mhanni A, Myers T, Proud V, Vergano S, Spangler B, Farrow E, Kussman J, Safina N; et al.

Hum Mutat. 2017 May;38(5):511-516. doi: 10.1002/humu.23196. Epub 2017 Mar 6.

PubMed [citation]

PMID:: 28185376

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From OMIM, SCV000692463.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

For discussion of the c.22C-T transition (c.22C-T, NM_017646.4) in the TRIT1 gene, resulting in an arg8-to-ter (R8X) substitution, that was found in compound heterozygous state in 2 sibs with combined oxidative phosphorylation deficiency-35 (COXPD35; 617873) by Kernohan et al. (2017), see 617840.0005.

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

From SIB Swiss Institute of Bioinformatics, SCV000883202.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	curation	PubMed (2)

Description

This variant is interpreted as Likely Pathogenic, for Combined oxidative phosphorylation deficiency 35, autosomal recessive. The following ACMG Tag(s) were applied: PM2-Supporting => PM2 downgraded in strength to Supporting. PVS1-Strong => PVS1 downgraded in strength to Strong. PP1 => Cosegregation with disease in multiple affected family members in a gene definitively known to cause the disease (https://www.ncbi.nlm.nih.gov/pubmed/28185376).

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

From Baylor Genetics, SCV005049810.1

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

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

Last Updated: Sep 29, 2024

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