NM_001267550.2(TTN):c.76922G>A (p.Arg25641His) AND not specified

Germline classification:: Benign/Likely benign (5 submissions)
Last evaluated:: Feb 12, 2022
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:: RCV000223093.13

Allele description [Variation Report for NM_001267550.2(TTN):c.76922G>A (p.Arg25641His)]

NM_001267550.2(TTN):c.76922G>A (p.Arg25641His)

Genes:

TTN-AS1:TTN antisense RNA 1 [Gene - HGNC]
TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.76922G>A (p.Arg25641His)

Other names:

p.R24000H:CGT>CAT

HGVS:

NC_000002.12:g.178569210C>T
NG_011618.3:g.266593G>A
NG_051363.1:g.51384C>T
NM_001256850.1:c.71999G>A
NM_001267550.2:c.76922G>AMANE SELECT
NM_003319.4:c.49727G>A
NM_133378.4:c.69218G>A
NM_133432.3:c.50102G>A
NM_133437.4:c.50303G>A
NP_001243779.1:p.Arg24000His
NP_001254479.2:p.Arg25641His
NP_003310.4:p.Arg16576His
NP_596869.4:p.Arg23073His
NP_597676.3:p.Arg16701His
NP_597681.4:p.Arg16768His
LRG_391t1:c.76922G>A
LRG_391:g.266593G>A
NC_000002.11:g.179433937C>T
NM_001267550.1:c.76922G>A
NM_003319.4:c.49727G>A

Protein change:

R16576H

Links:

dbSNP: rs369707906

NCBI 1000 Genomes Browser:

rs369707906

Molecular consequence:

NM_001256850.1:c.71999G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.76922G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.49727G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.69218G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.50102G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.50303G>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
SCV000237562	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Aug 24, 2016)	germline	clinical testing	Citation Link,
SCV000271081	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely benign (Apr 29, 2015)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000335015	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Likely benign (Sep 15, 2015)	germline	clinical testing	Citation Link,
SCV001917353	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
SCV002104068	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Feb 12, 2022)	germline	clinical testing	Citation Link

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	not provided	1	1	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	1	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

Details of each submission

From GeneDx, SCV000237562.6

#	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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000271081.3

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

Description

p.Arg23073His in exon 275 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.64% (100/15620) of South Asian chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitut e.org; dbSNP rs369707906).

#	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		1	not provided	1	not provided

From Eurofins Ntd Llc (ga), SCV000335015.4

#	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 Clinical Genetics, Academic Medical Center - VKGL Data-share Consensus, SCV001917353.1

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002104068.1

#	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

Last Updated: Apr 15, 2024

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