NM_003280.3(TNNC1):c.322_338del (p.Ala108fs) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 19, 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:: RCV002825462.2

Allele description [Variation Report for NM_003280.3(TNNC1):c.322_338del (p.Ala108fs)]

NM_003280.3(TNNC1):c.322_338del (p.Ala108fs)

Gene:

TNNC1:troponin C1, slow skeletal and cardiac type [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

3p21.1

Genomic location:

Preferred name:

NM_003280.3(TNNC1):c.322_338del (p.Ala108fs)

HGVS:

NC_000003.12:g.52451507_52451523del
NG_008963.1:g.7519_7535del
NG_033112.1:g.1000_1016del
NG_033112.2:g.905_921del
NM_003280.3:c.322_338delMANE SELECT
NP_003271.1:p.Ala108Profs
NP_003271.1:p.Ala108fs
LRG_378t1:c.322_338del17
LRG_378:g.7519_7535del
LRG_378p1:p.Ala108Profs
NC_000003.11:g.52485523_52485539del
NM_003280.2:c.322_338del17

Protein change:

A108fs

Molecular consequence:

NM_003280.3:c.322_338del - frameshift variant - [Sequence Ontology: SO:0001589]

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
SCV003209166	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 19, 2022)	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

SCV003209166

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 19, 2022)

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):240-242.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Invitae, SCV003209166.2

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

Description

This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Ala108Profs*3) in the TNNC1 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in TNNC1 cause disease. This variant has not been reported in the literature in individuals affected with TNNC1-related conditions. 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: Feb 28, 2024

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