NM_001276345.2(TNNT2):c.310C>A (p.Arg104Ser) AND Hypertrophic cardiomyopathy 2

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 19, 2020
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:: RCV003225686.2

Allele description [Variation Report for NM_001276345.2(TNNT2):c.310C>A (p.Arg104Ser)]

NM_001276345.2(TNNT2):c.310C>A (p.Arg104Ser)

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.310C>A (p.Arg104Ser)

HGVS:

NC_000001.11:g.201365292G>T
NG_007556.1:g.17386C>A
NM_000364.3:c.310C>A
NM_000364.4:c.310C>A
NM_001001430.3:c.280C>A
NM_001001431.3:c.280C>A
NM_001001432.3:c.265C>A
NM_001276345.2:c.310C>AMANE SELECT
NM_001276346.2:c.291+318C>A
NM_001276347.2:c.280C>A
NM_001406723.1:c.310C>A
NM_001406724.1:c.280C>A
NM_001406725.1:c.277C>A
NM_001406726.1:c.280C>A
NM_001406727.1:c.280C>A
NM_001406728.1:c.265C>A
NP_000355.2:p.Arg104Ser
NP_001001430.1:p.Arg94Ser
NP_001001431.1:p.Arg94Ser
NP_001001432.1:p.Arg89Ser
NP_001263274.1:p.Arg104Ser
NP_001263276.1:p.Arg94Ser
NP_001393652.1:p.Arg104Ser
NP_001393653.1:p.Arg94Ser
NP_001393654.1:p.Arg93Ser
NP_001393655.1:p.Arg94Ser
NP_001393656.1:p.Arg94Ser
NP_001393657.1:p.Arg89Ser
LRG_431t1:c.310C>A
LRG_431:g.17386C>A
LRG_431p1:p.Arg104Ser
NC_000001.10:g.201334420G>T
NM_000364.2:c.310C>A

Protein change:

R104S

Molecular consequence:

NM_001276346.2:c.291+318C>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000364.4:c.310C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001001430.3:c.280C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001001431.3:c.280C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001001432.3:c.265C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276345.2:c.310C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001276347.2:c.280C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406723.1:c.310C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406724.1:c.280C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406725.1:c.277C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406726.1:c.280C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406727.1:c.280C>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001406728.1:c.265C>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
SCV003921965	Victorian Clinical Genetics Services, Murdoch Childrens Research Institute See additional submitters Shariant Australia, Australian Genomics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 19, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 18612386, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003921965

Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 19, 2020)

germline

clinical testing

PubMed (2)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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

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 Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV003921965.2

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

Description

Based on the classification scheme VCGS_Germline_v1.3.3, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative and gain of function are reported mechanisms of disease in this gene and is 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 serine. (I) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0501 - Missense variant consistently predicted to be damaging by multiple in silico tools or highly conserved with a major amino acid change. (SP) 0601 - Variant is located in the well-established functional Troponin domain (PDB, NCBI). (SP) 0702 - Other missense variants comparable to the one identified in this case have strong previous evidence for pathogenicity. Three different variants in the same codon resulting in changes to a cysteine, histidine, leucine has also been reported as pathogenic in ClinVar. (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) 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

Last Updated: Aug 4, 2024

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