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NM_001267550.2(TTN):c.80774G>A (p.Arg26925Lys) AND not specified

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
May 27, 2025
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV000604866.5

Allele description [Variation Report for NM_001267550.2(TTN):c.80774G>A (p.Arg26925Lys)]

NM_001267550.2(TTN):c.80774G>A (p.Arg26925Lys)

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.80774G>A (p.Arg26925Lys)
HGVS:
  • NC_000002.12:g.178565358C>T
  • NG_011618.3:g.270445G>A
  • NG_051363.1:g.47532C>T
  • NM_001256850.1:c.75851G>A
  • NM_001267550.2:c.80774G>AMANE SELECT
  • NM_003319.4:c.53579G>A
  • NM_133378.4:c.73070G>A
  • NM_133432.3:c.53954G>A
  • NM_133437.4:c.54155G>A
  • NP_001243779.1:p.Arg25284Lys
  • NP_001254479.2:p.Arg26925Lys
  • NP_003310.4:p.Arg17860Lys
  • NP_596869.4:p.Arg24357Lys
  • NP_597676.3:p.Arg17985Lys
  • NP_597681.4:p.Arg18052Lys
  • LRG_391:g.270445G>A
  • NC_000002.11:g.179430085C>T
  • NM_001267550.2:c.80774G>A
Protein change:
R17860K
Links:
dbSNP: rs748215561
NCBI 1000 Genomes Browser:
rs748215561
Molecular consequence:
  • NM_001256850.1:c.75851G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.80774G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.53579G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.73070G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.53954G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.54155G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000712245Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Uncertain significance
(Jun 16, 2016) 		germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

SCV006087344Women's Health and Genetics/Laboratory Corporation of America, LabCorp
criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)		Uncertain significance
(May 27, 2025) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

A systematic approach to assessing the clinical significance of genetic variants.

Duzkale H, Shen J, McLaughlin H, Alfares A, Kelly MA, Pugh TJ, Funke BH, Rehm HL, Lebo MS.

Clin Genet. 2013 Nov;84(5):453-63. doi: 10.1111/cge.12257.

PubMed [citation]
PMID:
24033266
PMCID:
PMC3995020

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000712245.2

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

Description

The p.Arg24357Lys variant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 2/66698 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP r s748215561). Computational prediction tools and conservation analysis do not pro vide strong support for or against an impact to the protein. In summary, the cli nical significance of the p.Arg24357Lys variant is uncertain.

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV006087344.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: TTN c.73070G>A (p.Arg24357Lys) results in a conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change. The variant allele was found at a frequency of 2e-05 in 248604 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.73070G>A in individuals affected with Autosomal Recessive Titinopathy and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 505123). Based on the evidence outlined above, the variant was classified as uncertain significance.

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

Last Updated: Aug 16, 2025