NM_001267550.2(TTN):c.35794G>T (p.Glu11932Ter) AND Myopathy, early-onset, with fatal cardiomyopathy

Clinical significance:Uncertain significance

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000663407.1

Allele description [Variation Report for NM_001267550.2(TTN):c.35794G>T (p.Glu11932Ter)]

NM_001267550.2(TTN):c.35794G>T (p.Glu11932Ter)

Gene:
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.35794G>T (p.Glu11932Ter)
HGVS:
  • NC_000002.12:g.178667239C>A
  • NG_011618.3:g.168564G>T
  • NM_001256850.1:c.34264+2979G>T
  • NM_001267550.2:c.35794G>TMANE SELECT
  • NM_003319.4:c.13283-24922G>T
  • NM_133378.4:c.31483+2979G>T
  • NM_133432.3:c.13658-24922G>T
  • NM_133437.4:c.13859-24922G>T
  • NP_001254479.2:p.Glu11932Ter
  • LRG_391:g.168564G>T
  • NC_000002.11:g.179531966C>A
Protein change:
E11932*
Links:
dbSNP: rs878854299
NCBI 1000 Genomes Browser:
rs878854299
Molecular consequence:
  • NM_001256850.1:c.34264+2979G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_003319.4:c.13283-24922G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133378.4:c.31483+2979G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133432.3:c.13658-24922G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133437.4:c.13859-24922G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001267550.2:c.35794G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Myopathy, early-onset, with fatal cardiomyopathy (SALMY)
Synonyms:
Salih Myopathy
Identifiers:
MONDO: MONDO:0012714; MedGen: C2673677; Orphanet: 289377; OMIM: 611705

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000786695Broad Institute Rare Disease Group, Broad Institute - Broad Institute Center for Mendelian Genomics (CMG)criteria provided, single submitter
Uncertain significancegermlineresearch

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
Unspecifiedgermlineyes11not providednot providednot providedresearch

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Broad Institute Rare Disease Group, Broad Institute - Broad Institute Center for Mendelian Genomics (CMG), SCV000786695.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1Unspecified1not providednot providedresearch PubMed (1)

Description

The heterozygous p.Glu11932X variant in TTN has been identified in the compound heterozygous state by our project in one individual with early onset myopathy. The p.Glu11932X variant has not been reported in the literature however, it has been reported as a VUS for dilated cardiomyopathy in ClinVar. The lab reportedly identified this variant in 2 individuals, though no additional evidence was provided. Compound heterozygous loss of function TTN variants have been reported in individuals with early onset myopathy and cardiomyopathy. This variant has been identified in <0.01% (2/92728) of European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs768073446). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. In summary, while the predicted impact of this variant provides some suspicion for a pathogenic role, the clinical significance of the p.Glu11932X variant is uncertain.

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

Last Updated: Jul 10, 2021

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