NM_001276345.2(TNNT2):c.418C>T (p.Arg140Cys) AND Hypertrophic cardiomyopathy 2

Germline classification:: Pathogenic/Likely pathogenic (2 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:: RCV002470730.2

Allele description [Variation Report for NM_001276345.2(TNNT2):c.418C>T (p.Arg140Cys)]

NM_001276345.2(TNNT2):c.418C>T (p.Arg140Cys)

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.418C>T (p.Arg140Cys)

Other names:

p.R130C:CGT>TGT

HGVS:

NC_000001.11:g.201364369G>A
NG_007556.1:g.18309C>T
NM_000364.4:c.418C>T
NM_001001430.3:c.388C>T
NM_001001431.3:c.388C>T
NM_001001432.3:c.373C>T
NM_001276345.2:c.418C>TMANE SELECT
NM_001276346.2:c.298C>T
NM_001276347.2:c.388C>T
NP_000355.2:p.Arg140Cys
NP_001001430.1:p.Arg130Cys
NP_001001431.1:p.Arg130Cys
NP_001001432.1:p.Arg125Cys
NP_001263274.1:p.Arg140Cys
NP_001263275.1:p.Arg100Cys
NP_001263276.1:p.Arg130Cys
LRG_431t1:c.418C>T
LRG_431:g.18309C>T
LRG_431p1:p.Arg140Cys
NC_000001.10:g.201333497G>A
NM_000364.3:c.418C>T
NM_001001430.1:c.388C>T
NM_001001430.2:c.388C>T
NM_001001430.3:c.388C>T
c.388C>T

Protein change:

R100C

Links:

dbSNP: rs397516463

NCBI 1000 Genomes Browser:

rs397516463

Molecular consequence:

NM_000364.4:c.418C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001001430.3:c.388C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001001431.3:c.388C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001001432.3:c.373C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276345.2:c.418C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276346.2:c.298C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001276347.2:c.388C>T - 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
SCV002767830	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (May 6, 2021)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 15563892, 18612386, 25524337, 28973951, 25741868
SCV004181421	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

SCV002767830

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(May 6, 2021)

germline

clinical testing

PubMed (5)
[See all records that cite these PMIDs]

SCV004181421

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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Mutations profile in Chinese patients with hypertrophic cardiomyopathy.

Song L, Zou Y, Wang J, Wang Z, Zhen Y, Lou K, Zhang Q, Wang X, Wang H, Li J, Hui R.

Clin Chim Acta. 2005 Jan;351(1-2):209-16.

PubMed [citation]

PMID:: 15563892

The role of cardiac troponin T quantity and function in cardiac development and dilated cardiomyopathy.

Ahmad F, Banerjee SK, Lage ML, Huang XN, Smith SH, Saba S, Rager J, Conner DA, Janczewski AM, Tobita K, Tinney JP, Moskowitz IP, Perez-Atayde AR, Keller BB, Mathier MA, Shroff SG, Seidman CE, Seidman JG.

PLoS One. 2008 Jul 9;3(7):e2642. doi: 10.1371/journal.pone.0002642.

PubMed [citation]

PMID:: 18612386
PMCID:: PMC2441440

See all PubMed Citations (5)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV002767830.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Pathogenic. Following criteria are met: 0103 - Loss of function and gain of function are known mechanisms of disease in this gene and are associated with hypertrophic cardiomyopathy 2 (MIM#115195) (PMID: 18612386). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0200 - Variant is predicted to result in a missense amino acid change from arginine to cysteine. (I) 0251 - This variant is heterozygous. (I) 0302 - Variant is present in gnomAD (v3) <0.001 for a dominant condition (2 heterozygotes, 0 homozygotes). (SP) 0309 - An alternative amino acid change at the same position has been observed in gnomAD (v2) (3 heterozygotes, 0 homozygotes). (I) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools and highly conserved with a major amino acid change. (SP) 0600 - Variant is located in the annotated troponin domain (NCBI, PDB). (I) 0801 - This variant has strong previous evidence of pathogenicity in unrelated individuals. The variant has previously been reported in multiple individuals and families with hypertrophic cardiomyopathy 2 (MIM#115195) (ClinVar, HGMD, PMIDs: 15563892, 25524337, 28973951). (SP) 1205 - This variant has been shown to be maternally inherited (by segregation testing). (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#	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, SCV004181421.1

#	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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