NM_001267550.2(TTN):c.25490G>A (p.Arg8497His) AND not specified

Germline classification:: Benign/Likely benign (7 submissions)
Last evaluated:: Jan 6, 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:: RCV000040029.27

Allele description [Variation Report for NM_001267550.2(TTN):c.25490G>A (p.Arg8497His)]

NM_001267550.2(TTN):c.25490G>A (p.Arg8497His)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.25490G>A (p.Arg8497His)

Other names:

p.R8180H:CGC>CAC

HGVS:

NC_000002.12:g.178717244C>T
NG_011618.3:g.118559G>A
NM_001256850.1:c.24539G>A
NM_001267550.2:c.25490G>AMANE SELECT
NM_003319.4:c.13282+20838G>A
NM_133378.4:c.21758G>A
NM_133432.3:c.13657+20838G>A
NM_133437.4:c.13858+20838G>A
NP_001243779.1:p.Arg8180His
NP_001254479.2:p.Arg8497His
NP_596869.4:p.Arg7253His
NP_596869.4:p.Arg7253His
LRG_391t1:c.25490G>A
LRG_391:g.118559G>A
NC_000002.11:g.179581971C>T
NM_001267550.1:c.25490G>A
c.21758G>A

Protein change:

R7253H

Links:

dbSNP: rs149855485

NCBI 1000 Genomes Browser:

rs149855485

Molecular consequence:

NM_003319.4:c.13282+20838G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_133432.3:c.13657+20838G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_133437.4:c.13858+20838G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001256850.1:c.24539G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.25490G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.21758G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

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
SCV000063720	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Benign (Feb 25, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000238363	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Feb 8, 2016)	germline	clinical testing	Citation Link,
SCV000334890	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Benign (Sep 1, 2015)	germline	clinical testing	Citation Link,
SCV001337902	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Jan 6, 2020)	germline	clinical testing	Citation Link,
SCV001476321	Athena Diagnostics	criteria provided, single submitter (Athena Diagnostics Criteria)	Benign (Nov 5, 2019)	unknown	clinical testing	PubMed (3) [See all records that cite these PMIDs] 25163546, 23861362, 26467025
SCV001923544	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
SCV001957533	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - 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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	13	13	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

Atlas of the clinical genetics of human dilated cardiomyopathy.

Haas J, Frese KS, Peil B, Kloos W, Keller A, Nietsch R, Feng Z, Müller S, Kayvanpour E, Vogel B, Sedaghat-Hamedani F, Lim WK, Zhao X, Fradkin D, Köhler D, Fischer S, Franke J, Marquart S, Barb I, Li DT, Amr A, Ehlermann P, et al.

Eur Heart J. 2015 May 7;36(18):1123-35a. doi: 10.1093/eurheartj/ehu301. Epub 2014 Aug 27.

PubMed [citation]

PMID:: 25163546

See all PubMed Citations (4)

Details of each submission

From Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000063720.6

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	13	not provided	not provided	clinical testing	PubMed (1)

Description

p.Arg7253His in exon 85 of TTN: This variant is not expected to have clinical si gnificance because it has been identified in 2.3% (383/16508) of South Asian chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs149855485).

#	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		13	not provided	13	not provided

From GeneDx, SCV000238363.6

#	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 Eurofins Ntd Llc (ga), SCV000334890.3

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

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001337902.1

#	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	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Athena Diagnostics, SCV001476321.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

#	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		not provided	not provided	not provided	not provided

From Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001923544.1

#	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 Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ - VKGL Data-share Consensus, SCV001957533.1

#	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: Dec 7, 2024

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