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NM_001267550.2(TTN):c.56051G>A (p.Cys18684Tyr) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
May 9, 2017
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:
RCV000549572.3

Allele description [Variation Report for NM_001267550.2(TTN):c.56051G>A (p.Cys18684Tyr)]

NM_001267550.2(TTN):c.56051G>A (p.Cys18684Tyr)

Genes:
TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.56051G>A (p.Cys18684Tyr)
HGVS:
  • NC_000002.12:g.178599850C>T
  • NG_011618.3:g.235953G>A
  • NG_051363.1:g.82024C>T
  • NM_001256850.1:c.51128G>A
  • NM_001267550.2:c.56051G>AMANE SELECT
  • NM_003319.4:c.28856G>A
  • NM_133378.4:c.48347G>A
  • NM_133432.3:c.29231G>A
  • NM_133437.4:c.29432G>A
  • NP_001243779.1:p.Cys17043Tyr
  • NP_001254479.2:p.Cys18684Tyr
  • NP_003310.4:p.Cys9619Tyr
  • NP_596869.4:p.Cys16116Tyr
  • NP_597676.3:p.Cys9744Tyr
  • NP_597681.4:p.Cys9811Tyr
  • LRG_391:g.235953G>A
  • NC_000002.11:g.179464577C>T
Protein change:
C16116Y
Links:
dbSNP: rs1025426023
NCBI 1000 Genomes Browser:
rs1025426023
Molecular consequence:
  • NM_001256850.1:c.51128G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.56051G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.28856G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.48347G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.29231G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.29432G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Dilated cardiomyopathy 1G (CMD1G)
Identifiers:
MONDO: MONDO:0011400; MedGen: C1858763; Orphanet: 154; OMIM: 604145
Name:
Autosomal recessive limb-girdle muscular dystrophy type 2J (LGMDR10)
Synonyms:
Limb-girdle muscular dystrophy, type 2J; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 10
Identifiers:
MONDO: MONDO:0012127; MedGen: C1837342; Orphanet: 140922; OMIM: 608807

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000643390Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(May 9, 2017)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease.

Roberts AM, Ware JS, Herman DS, Schafer S, Baksi J, Bick AG, Buchan RJ, Walsh R, John S, Wilkinson S, Mazzarotto F, Felkin LE, Gong S, MacArthur JA, Cunningham F, Flannick J, Gabriel SB, Altshuler DM, Macdonald PS, Heinig M, Keogh AM, Hayward CS, et al.

Sci Transl Med. 2015 Jan 14;7(270):270ra6. doi: 10.1126/scitranslmed.3010134.

PubMed [citation]
PMID:
25589632
PMCID:
PMC4560092

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, SCV000643390.2

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

Description

This sequence change replaces cysteine with tyrosine at codon 18684 of the TTN protein (p.Cys18684Tyr). Conservation data is not available for the cysteine residue and there is a large physicochemical difference between cysteine and tyrosine. This variant also falls at the first nucleotide of exon 289 of the TTN coding sequence, which is part of the consensus splice site for this exon. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a TTN-related disease. This variant identified in the TTN gene is located in the A-band of the resulting protein (PMID: 25589632). Experimental studies and prediction algorithms are not available for this variant, and it is unclear how this variant impacts the function of this protein. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may alter RNA splicing, but this prediction has not been confirmed by published transcriptional studies. In summary, this variant is a novel missense change with uncertain impact on RNA splicing and protein function. It has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024