NM_003280.3(TNNC1):c.430A>G (p.Asn144Asp) AND multiple conditions

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 30, 2024
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:: RCV000471611.14

Allele description [Variation Report for NM_003280.3(TNNC1):c.430A>G (p.Asn144Asp)]

NM_003280.3(TNNC1):c.430A>G (p.Asn144Asp)

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.430A>G (p.Asn144Asp)

Other names:

p.N144D:AAC>GAC

HGVS:

NC_000003.12:g.52451415T>C
NG_008963.1:g.7627A>G
NG_033112.1:g.908T>C
NM_003280.3:c.430A>GMANE SELECT
NP_003271.1:p.Asn144Asp
LRG_378t1:c.430A>G
LRG_378:g.7627A>G
NC_000003.11:g.52485431T>C
NM_003280.2:c.430A>G

Protein change:

N144D

Links:

dbSNP: rs730881061

NCBI 1000 Genomes Browser:

rs730881061

Molecular consequence:

NM_003280.3:c.430A>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dilated cardiomyopathy 1Z (CMD1Z)
Identifiers:: MONDO: MONDO:0012745; MedGen: C2678475; Orphanet: 154; OMIM: 611879

Name:: Hypertrophic cardiomyopathy 13
Synonyms:: Familial hypertrophic cardiomyopathy 13; TNNC1-Related Familial Hypertrophic Cardiomyopathy
Identifiers:: MONDO: MONDO:0013195; MedGen: C2750472; OMIM: 613243

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000550242	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 30, 2024)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 29255176, 30165862, 30847666, 31513939, 32880476, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000550242

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 30, 2024)

germline

clinical testing

PubMed (6)
[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

Repeat genetic testing with targeted capture sequencing in primary arrhythmia syndrome and cardiomyopathy.

Robyns T, Kuiperi C, Breckpot J, Devriendt K, Souche E, Van Cleemput J, Willems R, Nuyens D, Matthijs G, Corveleyn A.

Eur J Hum Genet. 2017 Dec;25(12):1313-1323. doi: 10.1038/s41431-017-0004-3. Epub 2017 Oct 10.

PubMed [citation]

PMID:: 29255176
PMCID:: PMC5865127

Molecular analysis of inherited cardiomyopathy using next generation semiconductor sequencing technologies.

Lu C, Wu W, Liu F, Yang K, Li J, Liu Y, Wang R, Si N, Gao P, Liu Y, Zhang S, Zhang X.

J Transl Med. 2018 Aug 30;16(1):241. doi: 10.1186/s12967-018-1605-5.

PubMed [citation]

PMID:: 30165862
PMCID:: PMC6117967

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV000550242.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

This sequence change replaces asparagine, which is neutral and polar, with aspartic acid, which is acidic and polar, at codon 144 of the TNNC1 protein (p.Asn144Asp). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with dilated cardiomyopathy and/or hypertrophic cardiomyopathy (PMID: 29255176, 30165862, 30847666, 31513939, 32880476). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 181567). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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: May 12, 2024

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