NM_001276345.2(TNNT2):c.398T>G (p.Leu133Arg) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Apr 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:: RCV001368245.7

Allele description [Variation Report for NM_001276345.2(TNNT2):c.398T>G (p.Leu133Arg)]

NM_001276345.2(TNNT2):c.398T>G (p.Leu133Arg)

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.398T>G (p.Leu133Arg)

HGVS:

NC_000001.11:g.201365204A>C
NG_007556.1:g.17474T>G
NM_000364.4:c.398T>G
NM_001001430.3:c.368T>G
NM_001001431.3:c.368T>G
NM_001001432.3:c.353T>G
NM_001276345.2:c.398T>GMANE SELECT
NM_001276346.2:c.291+406T>G
NM_001276347.2:c.368T>G
NP_000355.2:p.Leu133Arg
NP_001001430.1:p.Leu123Arg
NP_001001431.1:p.Leu123Arg
NP_001001432.1:p.Leu118Arg
NP_001263274.1:p.Leu133Arg
NP_001263276.1:p.Leu123Arg
LRG_431t1:c.398T>G
LRG_431:g.17474T>G
LRG_431p1:p.Leu133Arg
NC_000001.10:g.201334332A>C

Protein change:

L118R

Links:

dbSNP: rs2102260711

NCBI 1000 Genomes Browser:

rs2102260711

Molecular consequence:

NM_001276346.2:c.291+406T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_000364.4:c.398T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001001430.3:c.368T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001001431.3:c.368T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001001432.3:c.353T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276345.2:c.398T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001276347.2:c.368T>G - 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

Name:: Dilated cardiomyopathy 1D
Synonyms:: Left ventricular noncompaction 6
Identifiers:: MONDO: MONDO:0011095; MedGen: C1832243; Orphanet: 154; Orphanet: 54260; OMIM: 601494

Name:: Cardiomyopathy, familial restrictive, 3
Identifiers:: MONDO: MONDO:0012900; MedGen: C2676271; Orphanet: 75249; OMIM: 612422

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001564631	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Apr 19, 2020)	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

SCV001564631

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Apr 19, 2020)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001564631.4

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

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with TNNT2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with arginine at codon 123 of the TNNT2 protein (p.Leu123Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine.

#	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: Sep 29, 2024

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