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NM_133379.5(TTN):c.15122C>G (p.Thr5041Arg) AND not specified

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Jan 30, 2015
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:
RCV000217022.7

Allele description [Variation Report for NM_133379.5(TTN):c.15122C>G (p.Thr5041Arg)]

NM_133379.5(TTN):c.15122C>G (p.Thr5041Arg)

Genes:
LOC126806432:CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:179611985-179613184 [Gene]
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_133379.5(TTN):c.15122C>G (p.Thr5041Arg)
Other names:
p.T5041R:ACA>AGA
HGVS:
  • NC_000002.12:g.178747278G>C
  • NG_011618.3:g.88525C>G
  • NM_001256850.1:c.10361-5357C>G
  • NM_001267550.2:c.11312-5357C>GMANE SELECT
  • NM_003319.4:c.10223-5357C>G
  • NM_133378.4:c.10360+5846C>G
  • NM_133379.5:c.15122C>G
  • NM_133432.3:c.10598-5357C>G
  • NM_133437.4:c.10799-5357C>G
  • NP_596870.2:p.Thr5041Arg
  • LRG_391:g.88525C>G
  • NC_000002.11:g.179612005G>C
  • NM_133379.3:c.15122C>G
  • NM_133379.5:c.15122C>G
Protein change:
T5041R
Links:
dbSNP: rs148791107
NCBI 1000 Genomes Browser:
rs148791107
Molecular consequence:
  • NM_001256850.1:c.10361-5357C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001267550.2:c.11312-5357C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_003319.4:c.10223-5357C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133378.4:c.10360+5846C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133432.3:c.10598-5357C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133437.4:c.10799-5357C>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133379.5:c.15122C>G - 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
SCV000238137GeneDx
criteria provided, single submitter

(GeneDx Variant Classification (06012015))		Uncertain significance
(Apr 7, 2014) 		germlineclinical testing

Citation Link,

SCV000272855Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine
criteria provided, single submitter

(LMM Criteria)		Uncertain significance
(Jan 30, 2015) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not providednot providednot providedclinical testing
not providedgermlineyesnot 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 GeneDx, SCV000238137.6

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

Description

Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in CARDIOMYOPATHY panel(s).

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

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000272855.3

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

Description

The p.Thr5041Arg variant in TTN has not been previously reported in individuals with cardiomyopathy but has been identified in 3/10496 of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP r s148791107). Computational prediction tools and conservation analysis are limit ed or unavailable for this variant. In summary, the clinical significance of the p.Thr5041Arg variant is uncertain.

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

Last Updated: Dec 24, 2023