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NM_003280.3(TNNC1):c.436G>A (p.Gly146Ser) AND Cardiovascular phenotype

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 12, 2022
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:
RCV002331620.1

Allele description

NM_003280.3(TNNC1):c.436G>A (p.Gly146Ser)

Gene:
TNNC1:troponin C1, slow skeletal and cardiac type [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
3p21.1
Genomic location:
Preferred name:
NM_003280.3(TNNC1):c.436G>A (p.Gly146Ser)
HGVS:
  • NC_000003.12:g.52451409C>T
  • NG_008963.1:g.7633G>A
  • NG_033112.1:g.902C>T
  • NM_003280.3:c.436G>AMANE SELECT
  • NP_003271.1:p.Gly146Ser
  • LRG_378t1:c.436G>A
  • LRG_378:g.7633G>A
  • NC_000003.11:g.52485425C>T
  • NM_003280.2:c.436G>A
Protein change:
G146S
Links:
dbSNP: rs567327895
NCBI 1000 Genomes Browser:
rs567327895
Molecular consequence:
  • NM_003280.3:c.436G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Cardiovascular phenotype
Identifiers:
MedGen: CN230736

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002628686Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Uncertain significance
(Oct 12, 2022) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Atlas of the clinical genetics of human dilated cardiomyopathy.

Haas J, Frese KS, Peil B, Kloos W, Keller A, Nietsch R, Feng Z, Müller S, Kayvanpour E, Vogel B, Sedaghat-Hamedani F, Lim WK, Zhao X, Fradkin D, Köhler D, Fischer S, Franke J, Marquart S, Barb I, Li DT, Amr A, Ehlermann P, et al.

Eur Heart J. 2015 May 7;36(18):1123-35a. doi: 10.1093/eurheartj/ehu301. Epub 2014 Aug 27.

PubMed [citation]
PMID:
25163546

Large next-generation sequencing gene panels in genetic heart disease: yield of pathogenic variants and variants of unknown significance.

van Lint FHM, Mook ORF, Alders M, Bikker H, Lekanne Dit Deprez RH, Christiaans I.

Neth Heart J. 2019 Jun;27(6):304-309. doi: 10.1007/s12471-019-1250-5.

PubMed [citation]
PMID:
30847666
PMCID:
PMC6533346

Details of each submission

From Ambry Genetics, SCV002628686.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (2)

Description

The p.G146S variant (also known as c.436G>A), located in coding exon 5 of the TNNC1 gene, results from a G to A substitution at nucleotide position 436. The glycine at codon 146 is replaced by serine, an amino acid with similar properties. This alteration has been reported in a dilated cardiomyopathy (DCM) cohort and an arrhythmia genetic testing cohort; however, clinical details were limited, and additional cardiac variants were detected in some cases (Haas J et al. Eur Heart J, 2015 May;36:1123-35a; van Lint FHM et al. Neth Heart J, 2019 Jun;27:304-309). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Mar 5, 2024