NM_001267550.2(TTN):c.3070G>A (p.Val1024Ile) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Aug 22, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000152517.2

Allele description [Variation Report for NM_001267550.2(TTN):c.3070G>A (p.Val1024Ile)]

NM_001267550.2(TTN):c.3070G>A (p.Val1024Ile)

Gene:
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.3070G>A (p.Val1024Ile)
HGVS:
  • NC_000002.12:g.178782836C>T
  • NG_011618.3:g.52967G>A
  • NM_001256850.1:c.3070G>A
  • NM_001267550.2:c.3070G>AMANE SELECT
  • NM_003319.4:c.2932G>A
  • NM_133378.4:c.3070G>A
  • NM_133379.5:c.3070G>A
  • NM_133432.3:c.2932G>A
  • NM_133437.4:c.2932G>A
  • NP_001243779.1:p.Val1024Ile
  • NP_001254479.2:p.Val1024Ile
  • NP_003310.4:p.Val978Ile
  • NP_596869.4:p.Val1024Ile
  • NP_596870.2:p.Val1024Ile
  • NP_597676.3:p.Val978Ile
  • NP_597681.4:p.Val978Ile
  • LRG_391:g.52967G>A
  • NC_000002.11:g.179647563C>T
Protein change:
V1024I
Links:
dbSNP: rs368770038
NCBI 1000 Genomes Browser:
rs368770038
Molecular consequence:
  • NM_001256850.1:c.3070G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.3070G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.2932G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.3070G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133379.5:c.3070G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.2932G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.2932G>A - 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
SCV000201703Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Jul 11, 2014)
germlineclinical testing

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

SCV000722334GeneDxcriteria provided, single submitter
Likely benign
(Aug 22, 2017)
germlineclinical testing

Citation Link

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 Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000201703.5

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

Description

Variant classified as Uncertain Significance - Favor Benign. The Val1024Ile vari ant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/4406 of African American chromosomes by the NHLBI E xome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs368770038). Valine (Val) at position 1024 is conserved in mammals, though several other spec ies (softshell turtle, spiny softshell turtle, tetradon, madaka, southern platyf ish, and zebrafish) have an isoleucine (Ile) at this position, raising the possi bility that this change may be tolerated. Additional computational prediction to ols do not provide strong support for or against an impact to the protein. In su mmary, while the clinical significance of the Val1024Ile variant is uncertain, t he presence of the variant amino acid in other species suggests that it is more likely to be benign.

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

From GeneDx, SCV000722334.1

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

Description

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.

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

Last Updated: Jul 7, 2021

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