NM_001267550.2(TTN):c.24431A>C (p.Glu8144Ala) AND not specified

Germline classification:: Benign/Likely benign (8 submissions)
Last evaluated:: Aug 16, 2020
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:: RCV000040001.24

Allele description [Variation Report for NM_001267550.2(TTN):c.24431A>C (p.Glu8144Ala)]

NM_001267550.2(TTN):c.24431A>C (p.Glu8144Ala)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.24431A>C (p.Glu8144Ala)

Other names:

p.E7827A:GAA>GCA

HGVS:

NC_000002.12:g.178718769T>G
NG_011618.3:g.117034A>C
NM_001256850.1:c.23480A>C
NM_001267550.2:c.24431A>CMANE SELECT
NM_003319.4:c.13282+19313A>C
NM_133378.4:c.20699A>C
NM_133432.3:c.13657+19313A>C
NM_133437.4:c.13858+19313A>C
NP_001243779.1:p.Glu7827Ala
NP_001254479.2:p.Glu8144Ala
NP_596869.4:p.Glu6900Ala
LRG_391t1:c.24431A>C
LRG_391:g.117034A>C
NC_000002.11:g.179583496T>G
NM_001267550.1:c.24431A>C
NM_001267550.2:c.24431A>C
c.20699A>C

Protein change:

E6900A

Links:

dbSNP: rs16866465

NCBI 1000 Genomes Browser:

rs16866465

Molecular consequence:

NM_003319.4:c.13282+19313A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_133432.3:c.13657+19313A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_133437.4:c.13858+19313A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_001256850.1:c.23480A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.24431A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.20699A>C - missense variant - [Sequence Ontology: SO:0001583]

Observations:

554

Condition(s)

Synonyms:: AllHighlyPenetrant
Identifiers:: MedGen: CN169374

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000051745	Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq	criteria provided, single submitter (Ng et al. (Circ Cardiovasc Genet. 2013))	Benign (Jun 24, 2013)	unknown	research	PubMed (1) [See all records that cite this PMID]
SCV000063692	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Benign (Apr 3, 2012)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000153205	Genetic Services Laboratory, University of Chicago	criteria provided, single submitter (ACMG Guidelines, 2007)	Benign (Aug 15, 2013)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000169633	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Oct 31, 2012)	germline	clinical testing	Citation Link,
SCV000315426	PreventionGenetics, part of Exact Sciences	criteria provided, single submitter (ACMG Guidelines, 2015)	Benign	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV001362583	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Aug 16, 2020)	germline	clinical testing	Citation Link,
SCV001922075	Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing
SCV001970775	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus See additional submitters Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	no assertion criteria provided	Benign	germline	clinical testing

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	556	554	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	207	not provided	not provided	not provided	not provided	research
not provided	germline	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Interpreting secondary cardiac disease variants in an exome cohort.

Ng D, Johnston JJ, Teer JK, Singh LN, Peller LC, Wynter JS, Lewis KL, Cooper DN, Stenson PD, Mullikin JC, Biesecker LG; NIH Intramural Sequencing Center (NISC) Comparative Sequencing Program..

Circ Cardiovasc Genet. 2013 Aug;6(4):337-46. doi: 10.1161/CIRCGENETICS.113.000039. Epub 2013 Jul 16.

PubMed [citation]

PMID:: 23861362
PMCID:: PMC3887521

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

See all PubMed Citations (4)

Details of each submission

From Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq, SCV000051745.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	207	not provided	not provided	research	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	unknown	not provided	not provided	not provided		207	not provided	not provided	not provided

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000063692.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	556	not provided	not provided	clinical testing	PubMed (1)

Description

Glu6900Ala in exon 81 of TTN: This variant is not expected to have clinical sign ificance because it has been identified in 14% (1033/6756) of European American chromosomes and 15% (470/3284) of African American chromosomes from a broad popu lation by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs16866465)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		556	not provided	554	not provided

From Genetic Services Laboratory, University of Chicago, SCV000153205.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1		not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From GeneDx, SCV000169633.11

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From PreventionGenetics, part of Exact Sciences, SCV000315426.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001362583.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001922075.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center - VKGL Data-share Consensus, SCV001970775.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

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