NM_001276345.2(TNNT2):c.305G>A (p.Arg102Gln) AND Hypertrophic cardiomyopathy 2

Germline classification:: Likely pathogenic (3 submissions)
Last evaluated:: Apr 11, 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:: RCV000013220.26

Allele description [Variation Report for NM_001276345.2(TNNT2):c.305G>A (p.Arg102Gln)]

NM_001276345.2(TNNT2):c.305G>A (p.Arg102Gln)

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.305G>A (p.Arg102Gln)

Other names:

p.R92Q:CGG>CAG

HGVS:

NC_000001.11:g.201365297C>T
NG_007556.1:g.17381G>A
NM_000364.4:c.305G>A
NM_001001430.3:c.275G>A
NM_001001431.3:c.275G>A
NM_001001432.3:c.260G>A
NM_001276345.2:c.305G>AMANE SELECT
NM_001276346.2:c.291+313G>A
NM_001276347.2:c.275G>A
NP_000355.2:p.Arg102Gln
NP_001001430.1:p.Arg92Gln
NP_001001431.1:p.Arg92Gln
NP_001001432.1:p.Arg87Gln
NP_001263274.1:p.Arg102Gln
NP_001263276.1:p.Arg92Gln
LRG_431t1:c.305G>A
LRG_431:g.17381G>A
LRG_431p1:p.Arg102Gln
NC_000001.10:g.201334425C>T
NM_001001430.1:c.275G>A
NM_001001430.2:c.275G>A
c.275G>A

Protein change:

R102Q; ARG92GLN

Links:

OMIM: 191045.0002; dbSNP: rs121964856

NCBI 1000 Genomes Browser:

rs121964856

Molecular consequence:

NM_001276346.2:c.291+313G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000364.4:c.305G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001001430.3:c.275G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001001431.3:c.275G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001001432.3:c.260G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276345.2:c.305G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276347.2:c.275G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Hypertrophic cardiomyopathy 2
Synonyms:: Familial hypertrophic cardiomyopathy 2; TNNT2-Related Familial Hypertrophic Cardiomyopathy
Identifiers:: MONDO: MONDO:0007266; MedGen: C1861864; OMIM: 115195

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000033467	OMIM	no assertion criteria provided	Pathogenic (Jun 3, 1994)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000299242	Center for Medical Genetics Ghent, University of Ghent	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Mar 8, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 8205619, 25741868
SCV004181493	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Apr 11, 2023)	germline	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

SCV000033467

OMIM

no assertion criteria provided

Pathogenic
(Jun 3, 1994)

germline

literature only

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

SCV000299242

Center for Medical Genetics Ghent, University of Ghent

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Mar 8, 2016)

germline

clinical testing

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

SCV004181493

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Apr 11, 2023)

germline

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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Alpha-tropomyosin and cardiac troponin T mutations cause familial hypertrophic cardiomyopathy: a disease of the sarcomere.

Thierfelder L, Watkins H, MacRae C, Lamas R, McKenna W, Vosberg HP, Seidman JG, Seidman CE.

Cell. 1994 Jun 3;77(5):701-12.

PubMed [citation]

PMID:: 8205619

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, SCV000033467.2

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

Description

In members of family BA with the form of familial hypertrophic cardiomyopathy (CMH2; 115195) linked to chromosome 1, Thierfelder et al. (1994) identified heterozygosity for a 287G-A transition in the TNNT2 gene, changing codon 92 from CGG to CAG and predicting the replacement of a positively charged arginine with a neutral glutamine (R92Q).

#	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 Center for Medical Genetics Ghent, University of Ghent, SCV000299242.2

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

Description

This variant has not been identified in large population databases (Gnomad, 1000 Genomes, Go NL, Exome Variant Server) and is predicted to have an impact on protein function according to multiple prediction programs. In addition, the variant has been reported previously in individuals with HCM. Studies have shown that the variant impacts protein function (PMID:8205619).

#	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 Genome-Nilou Lab, SCV004181493.1

#	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	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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