NM_001032283.3(TMPO):c.565+1328G>T AND not specified

Germline classification:: Uncertain significance (3 submissions)
Last evaluated:: Dec 9, 2024
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:: RCV000152054.8

Allele description [Variation Report for NM_001032283.3(TMPO):c.565+1328G>T]

NM_001032283.3(TMPO):c.565+1328G>T

Gene:

TMPO:thymopoietin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

12q23.1

Genomic location:

Preferred name:

NM_001032283.3(TMPO):c.565+1328G>T

HGVS:

NC_000012.12:g.98533166G>T
NG_021393.1:g.22594G>T
NM_001032283.3:c.565+1328G>TMANE SELECT
NM_001032284.3:c.565+1328G>T
NM_001307975.2:c.565+1328G>T
NM_003276.2:c.909G>T
NP_003267.1:p.Met303Ile
LRG_443t2:c.909G>T
LRG_443:g.22594G>T
LRG_443p2:p.Met303Ile
NC_000012.11:g.98926944G>T

Protein change:

M303I

Links:

dbSNP: rs369208265

NCBI 1000 Genomes Browser:

rs369208265

Molecular consequence:

NM_001032283.3:c.565+1328G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001032284.3:c.565+1328G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001307975.2:c.565+1328G>T - intron variant - [Sequence Ontology: SO:0001627]
NM_003276.2:c.909G>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000200665	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Dec 18, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV003911810	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Aug 1, 2024)	germline	clinical testing	Citation Link,
SCV005884704	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Uncertain significance (Dec 9, 2024)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000200665

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Dec 18, 2014)

germline

clinical testing

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

SCV003911810

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Aug 1, 2024)

germline

clinical testing

Citation Link,

SCV005884704

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Uncertain significance
(Dec 9, 2024)

germline

clinical testing

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	2	2	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

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]

PMID:: 24033266
PMCID:: PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000200665.5

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

Description

The p.Met303Ile variant in TMPO has been identified by our laboratory in 1 indiv idual with ischemic cardiomyopathy. This variant has also been identified in 2/6 7574 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac .broadinstitute.org; dbSNP rs369208265). Methionine (Met) at position 303 is not conserved in mammals or evolutionarily distant species and 1 mammal (squirrel m onkey) carries an isoleucine (Ile) at this position, raising the possibility tha t this change may be tolerated. Additional computational prediction tools also s uggest that the p.Met303Ile variant may not impact the protein, though this info rmation is not predictive enough to rule out pathogenicity. In summary, the clin ical significance of the p.Met303Ile variant is uncertain.

#	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		2	not provided	2	not provided

From Ambry Genetics, SCV003911810.3

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

Description

The c.909G>T (p.M303I) alteration is located in exon 4 (coding exon 4) of the TMPO gene. This alteration results from a G to T substitution at nucleotide position 909, causing the methionine (M) at amino acid position 303 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

#	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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005884704.1

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

#	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: Mar 22, 2025

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