NM_001276345.2(TNNT2):c.473G>A (p.Arg158Gln) AND Cardiovascular phenotype

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Nov 8, 2022
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:: RCV002326912.3

Allele description [Variation Report for NM_001276345.2(TNNT2):c.473G>A (p.Arg158Gln)]

NM_001276345.2(TNNT2):c.473G>A (p.Arg158Gln)

Gene:

TNNT2:troponin T2, cardiac type [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

1q32.1

Genomic location:

Preferred name:

NM_001276345.2(TNNT2):c.473G>A (p.Arg158Gln)

Other names:

p.R148Q:CGG>CAG

HGVS:

NC_000001.11:g.201364314C>T
NG_007556.1:g.18364G>A
NM_000364.4:c.473G>A
NM_001001430.3:c.443G>A
NM_001001431.3:c.443G>A
NM_001001432.3:c.428G>A
NM_001276345.2:c.473G>AMANE SELECT
NM_001276346.2:c.353G>A
NM_001276347.2:c.443G>A
NP_000355.2:p.Arg158Gln
NP_001001430.1:p.Arg148Gln
NP_001001431.1:p.Arg148Gln
NP_001001432.1:p.Arg143Gln
NP_001263274.1:p.Arg158Gln
NP_001263275.1:p.Arg118Gln
NP_001263276.1:p.Arg148Gln
LRG_431t1:c.473G>A
LRG_431:g.18364G>A
LRG_431p1:p.Arg158Gln
NC_000001.10:g.201333442C>T
NM_001001430.1:c.443G>A
NM_001276345.2:c.473G>A

Protein change:

R118Q

Links:

dbSNP: rs730881102

NCBI 1000 Genomes Browser:

rs730881102

Molecular consequence:

NM_000364.4:c.473G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001001430.3:c.443G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001001431.3:c.443G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001001432.3:c.428G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276345.2:c.473G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276346.2:c.353G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276347.2:c.443G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Cardiovascular phenotype
Identifiers:: MedGen: CN230736

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002632289	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Uncertain significance (Nov 8, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30565988, 31006259 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002632289

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Uncertain significance
(Nov 8, 2022)

germline

clinical testing

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

Citation Link

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

Functional Annotation of TNNT2 Variants of Uncertain Significance With Genome-Edited Cardiomyocytes.

Lv W, Qiao L, Petrenko N, Li W, Owens AT, McDermott-Roe C, Musunuru K.

Circulation. 2018 Dec 11;138(24):2852-2854. doi: 10.1161/CIRCULATIONAHA.118.035028. No abstract available.

PubMed [citation]

PMID:: 30565988
PMCID:: PMC6309910

Yield of Clinical Screening for Hypertrophic Cardiomyopathy in Child First-Degree Relatives.

Norrish G, Jager J, Field E, Quinn E, Fell H, Lord E, Cicerchia MN, Ochoa JP, Cervi E, Elliott PM, Kaski JP.

Circulation. 2019 Jul 16;140(3):184-192. doi: 10.1161/CIRCULATIONAHA.118.038846. Epub 2019 Apr 22.

PubMed [citation]

PMID:: 31006259
PMCID:: PMC6636798

Details of each submission

From Ambry Genetics, SCV002632289.3

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

Description

The p.R148Q variant (also known as c.443G>A), located in coding exon 9 of the TNNT2 gene, results from a G to A substitution at nucleotide position 443. The arginine at codon 148 is replaced by glutamine, an amino acid with highly similar properties. This variant was reported in a hypertrophic cardiomyopathy cohort; however, clinical details were limited (Norrish G et al. Circulation, 2019 Jul;140:184-192). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, 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

Last Updated: May 1, 2024

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