NM_001267550.2(TTN):c.18778A>C (p.Lys6260Gln) AND not specified

Clinical significance:Uncertain significance (Last evaluated: Apr 21, 2013)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000154989.1

Allele description [Variation Report for NM_001267550.2(TTN):c.18778A>C (p.Lys6260Gln)]

NM_001267550.2(TTN):c.18778A>C (p.Lys6260Gln)

Gene:
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.18778A>C (p.Lys6260Gln)
HGVS:
  • NC_000002.12:g.178729378T>G
  • NG_011618.3:g.106425A>C
  • NM_001256850.1:c.17827A>C
  • NM_001267550.2:c.18778A>CMANE SELECT
  • NM_003319.4:c.13282+8704A>C
  • NM_133378.4:c.15046A>C
  • NM_133432.3:c.13657+8704A>C
  • NM_133437.4:c.13858+8704A>C
  • NP_001243779.1:p.Lys5943Gln
  • NP_001254479.2:p.Lys6260Gln
  • NP_596869.4:p.Lys5016Gln
  • LRG_391:g.106425A>C
  • NC_000002.11:g.179594105T>G
Protein change:
K5016Q
Links:
dbSNP: rs375652574
NCBI 1000 Genomes Browser:
rs375652574
Molecular consequence:
  • NM_003319.4:c.13282+8704A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133432.3:c.13657+8704A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133437.4:c.13858+8704A>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001256850.1:c.17827A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.18778A>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.15046A>C - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000204671Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Apr 21, 2013)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenot provided11not 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, Partners HealthCare Personalized Medicine, SCV000204671.5

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

Description

Variant classified as Uncertain Significance - Favor Benign. The Lys5016Gln vari ant in TTN has not been reported in individuals with cardiomyopathy, but has bee n identified in 2/8278 European American chromosomes by the NHLBI Exome Sequenci ng Project (http://evs.gs.washington.edu/EVS/). Lysine (Lys) at position 5016 is not conserved in mammals, suggesting that a change at this position would be to lerated. Additional computational analyses (biochemical amino acid properties, A lignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an i mpact to the protein. Although the lack of segregation supports that the Lys5016 Gln variant may be benign, additional studies are needed to fully assess its cli nical significance.

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

Last Updated: Nov 27, 2021

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