NM_001953.5(TYMP):c.1310G>A (p.Trp437Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 16, 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:: RCV002016630.12

Allele description [Variation Report for NM_001953.5(TYMP):c.1310G>A (p.Trp437Ter)]

NM_001953.5(TYMP):c.1310G>A (p.Trp437Ter)

Genes:

LOC130067862:ATAC-STARR-seq lymphoblastoid silent region 13986 [Gene]
SCO2:synthesis of cytochrome C oxidase 2 [Gene - OMIM - HGNC]
TYMP:thymidine phosphorylase [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.33

Genomic location:

Preferred name:

NM_001953.5(TYMP):c.1310G>A (p.Trp437Ter)

HGVS:

NC_000022.11:g.50525909C>T
NG_011860.1:g.9177G>A
NG_016235.1:g.5531G>A
NG_021419.1:g.22694C>T
NG_202277.1:g.230C>T
NM_001113755.3:c.1310G>A
NM_001113756.3:c.1310G>A
NM_001169109.2:c.-14+337G>A
NM_001169110.1:c.-14+92G>A
NM_001257988.1:c.1310G>A
NM_001257989.1:c.1325G>A
NM_001953.5:c.1310G>AMANE SELECT
NP_001107227.1:p.Trp437Ter
NP_001107228.1:p.Trp437Ter
NP_001244917.1:p.Trp437Ter
NP_001244918.1:p.Trp442Ter
NP_001944.1:p.Trp437Ter
LRG_727t1:c.1310G>A
LRG_727t2:c.1325G>A
LRG_727:g.9177G>A
LRG_727p1:p.Trp437Ter
LRG_727p2:p.Trp442Ter
NC_000022.10:g.50964338C>T

Protein change:

W437*

Links:

dbSNP: rs1243213428

NCBI 1000 Genomes Browser:

rs1243213428

Molecular consequence:

NM_001169109.2:c.-14+337G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001169110.1:c.-14+92G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001113755.3:c.1310G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001113756.3:c.1310G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001257988.1:c.1310G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001257989.1:c.1325G>A - nonsense - [Sequence Ontology: SO:0001587]
NM_001953.5:c.1310G>A - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

Clear Turn Off Turn On

Chain A, Heme oxygenase 2
Chain A, Heme oxygenase 2
gi|159795483|pdb|2RGZ|A

Protein

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002298804	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 16, 2023)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15505189, 17437622, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002298804

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 16, 2023)

germline

clinical testing

PubMed (3)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Lack of gastrointestinal symptoms in a 60-year-old patient with MNGIE.

Martín MA, Blázquez A, Martí R, Bautista J, Lara MC, Cabello A, Campos Y, Belda O, Andreu AL, Arenas J.

Neurology. 2004 Oct 26;63(8):1536-7. No abstract available.

PubMed [citation]

PMID:: 15505189

Cognitive dysfunction and hypogonadotrophic hypogonadism in a Brazilian patient with mitochondrial neurogastrointestinal encephalomyopathy and a novel ECGF1 mutation.

Carod-Artal FJ, Herrero MD, Lara MC, López-Gallardo E, Ruiz-Pesini E, Martí R, Montoya J.

Eur J Neurol. 2007 May;14(5):581-5.

PubMed [citation]

PMID:: 17437622

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002298804.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

ClinVar contains an entry for this variant (Variation ID: 1511314). This sequence change creates a premature translational stop signal (p.Trp437*) in the TYMP gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 46 amino acid(s) of the TYMP protein. This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with mitochondrial neurogastrointestinal encephalomyopathy with other rare variant(s) present on the same allele (PMID: 15505189). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts a region of the TYMP protein in which other variant(s) (p.Ser471* ) have been determined to be pathogenic (PMID: 17437622). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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: Oct 26, 2024

ClinVar

Relating variation to medicine