NM_001276345.2(TNNT2):c.490-1G>C AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 13, 2023
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:: RCV002515088.3

Allele description [Variation Report for NM_001276345.2(TNNT2):c.490-1G>C]

NM_001276345.2(TNNT2):c.490-1G>C

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.490-1G>C

HGVS:

NC_000001.11:g.201363407C>G
NG_007556.1:g.19271G>C
NM_000364.4:c.490-1G>C
NM_001001430.3:c.460-1G>C
NM_001001431.3:c.460-1G>C
NM_001001432.3:c.445-1G>C
NM_001276345.2:c.490-1G>CMANE SELECT
NM_001276346.2:c.370-1G>C
NM_001276347.2:c.460-1G>C
NM_001406723.1:c.490-1G>C
NM_001406724.1:c.460-1G>C
NM_001406725.1:c.457-1G>C
NM_001406726.1:c.460-1G>C
NM_001406727.1:c.460-1G>C
NM_001406728.1:c.445-1G>C
LRG_431t1:c.490-1G>C
LRG_431:g.19271G>C
NC_000001.10:g.201332535C>G
NM_001001430.1:c.460-1G>C
NM_001001430.2:c.460-1G>C

Links:

dbSNP: rs111344408

NCBI 1000 Genomes Browser:

rs111344408

Molecular consequence:

NM_000364.4:c.490-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001001430.3:c.460-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001001431.3:c.460-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001001432.3:c.445-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276345.2:c.490-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276346.2:c.370-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001276347.2:c.460-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406723.1:c.490-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406724.1:c.460-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406725.1:c.457-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406726.1:c.460-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406727.1:c.460-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]
NM_001406728.1:c.445-1G>C - splice acceptor variant - [Sequence Ontology: SO:0001574]

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

Recent activity

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Human DNA sequence from clone RP11-789G22 on chromosome 13, complete sequence
Human DNA sequence from clone RP11-789G22 on chromosome 13, complete sequence
gi|14348445|emb|AL356257.14|

Nucleotide
Saimiri sciureus TRNP1 upstream 2 regulatory element genomic sequence
Saimiri sciureus TRNP1 upstream 2 regulatory element genomic sequence
gi|2034478284|gb|MW373699.1|

Nucleotide
BPI fold-containing family C protein isoform X2 [Heterocephalus glaber]
BPI fold-containing family C protein isoform X2 [Heterocephalus glaber]
gi|1196723623|ref|XP_021114007.1|

Protein
Isodon ternifolius voucher Suddee s.n. (K) external transcribed spacer and small...
Isodon ternifolius voucher Suddee s.n. (K) external transcribed spacer and small subunit ribosomal RNA gene, partial sequence
gi|2419842544|gb|OL423187.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003295480	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 13, 2023)	germline	clinical testing	PubMed (4) [See all records that cite these PMIDs] 16199547, 25524337, 27532257, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003295480

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 13, 2023)

germline

clinical testing

PubMed (4)
[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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Splicing in action: assessing disease causing sequence changes.

Baralle D, Baralle M.

J Med Genet. 2005 Oct;42(10):737-48. Review.

PubMed [citation]

PMID:: 16199547
PMCID:: PMC1735933

Clinical phenotype and outcome of hypertrophic cardiomyopathy associated with thin-filament gene mutations.

Coppini R, Ho CY, Ashley E, Day S, Ferrantini C, Girolami F, Tomberli B, Bardi S, Torricelli F, Cecchi F, Mugelli A, Poggesi C, Tardiff J, Olivotto I.

J Am Coll Cardiol. 2014 Dec 23;64(24):2589-2600. doi: 10.1016/j.jacc.2014.09.059.

PubMed [citation]

PMID:: 25524337
PMCID:: PMC4270453

See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003295480.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (4)

Description

This sequence change affects an acceptor splice site in intron 10 of the TNNT2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), however the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TNNT2 cause disease. This variant is present in population databases (rs111344408, gnomAD 0.007%). Disruption of this splice site has been observed in individual(s) with hypertrophic cardiomyopathy (HCM) (PMID: 25524337, 27532257). ClinVar contains an entry for this variant (Variation ID: 181619). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.

#	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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