NM_001267550.2(TTN):c.25087G>T (p.Ala8363Ser) AND not specified

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(2) (Last evaluated: Dec 1, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000040022.5

Allele description [Variation Report for NM_001267550.2(TTN):c.25087G>T (p.Ala8363Ser)]

NM_001267550.2(TTN):c.25087G>T (p.Ala8363Ser)

Gene:
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.25087G>T (p.Ala8363Ser)
Other names:
p.A8046S:GCA>TCA
HGVS:
  • NC_000002.12:g.178717787C>A
  • NG_011618.3:g.118016G>T
  • NM_001256850.1:c.24136G>T
  • NM_001267550.2:c.25087G>TMANE SELECT
  • NM_003319.4:c.13282+20295G>T
  • NM_133378.4:c.21355G>T
  • NM_133432.3:c.13657+20295G>T
  • NM_133437.4:c.13858+20295G>T
  • NP_001243779.1:p.Ala8046Ser
  • NP_001254479.2:p.Ala8363Ser
  • NP_596869.4:p.Ala7119Ser
  • LRG_391t1:c.25087G>T
  • LRG_391:g.118016G>T
  • NC_000002.11:g.179582514C>A
  • NM_001267550.1:c.25087G>T
  • c.21355G>T
Protein change:
A7119S
Links:
dbSNP: rs200972189
NCBI 1000 Genomes Browser:
rs200972189
Molecular consequence:
  • NM_003319.4:c.13282+20295G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133432.3:c.13657+20295G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_133437.4:c.13858+20295G>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001256850.1:c.24136G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.25087G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.21355G>T - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

Recent activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000063713Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicinecriteria provided, single submitter
Uncertain significance
(Mar 16, 2012)
germlineclinical testing

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

SCV000238358GeneDxcriteria provided, single submitter
Likely benign
(Dec 1, 2017)
germlineclinical testing

Citation Link,

SCV000616032Athena Diagnostics Inccriteria provided, single submitter
Uncertain significance
(Jun 20, 2017)
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
not providedgermlineyesnot providednot providednot 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

A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.

Karbassi I, Maston GA, Love A, DiVincenzo C, Braastad CD, Elzinga CD, Bright AR, Previte D, Zhang K, Rowland CM, McCarthy M, Lapierre JL, Dubois F, Medeiros KA, Batish SD, Jones J, Liaquat K, Hoffman CA, Jaremko M, Wang Z, Sun W, Buller-Burckle A, et al.

Hum Mutat. 2016 Jan;37(1):127-34. doi: 10.1002/humu.22918. Epub 2015 Oct 29.

PubMed [citation]
PMID:
26467025
PMCID:
PMC4737317

Details of each submission

From Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine, SCV000063713.6

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

Description

Variant classified as Uncertain Significance - Favor Benign. The Ala7119Ser vari ant in TTN has been identified in 0.2% (7/2996) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS). Computational analyses (biochemical amino acid properties, con servation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. While this frequency suggests that Ala7119Ser variant is more likely benign, it is too low to confidently rule out a disease c ausing role. Additional information is needed to fully assess its clinical signi ficance.

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

From GeneDx, SCV000238358.7

#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

From Athena Diagnostics Inc, SCV000616032.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jul 7, 2021

Support Center