NM_001267550.2(TTN):c.25481G>A (p.Arg8494Gln) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (6 submissions)
Last evaluated:: Aug 17, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000172687.18

Allele description [Variation Report for NM_001267550.2(TTN):c.25481G>A (p.Arg8494Gln)]

NM_001267550.2(TTN):c.25481G>A (p.Arg8494Gln)

Gene:

TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.25481G>A (p.Arg8494Gln)

HGVS:

NC_000002.12:g.178717253C>T
NG_011618.3:g.118550G>A
NM_001256850.1:c.24530G>A
NM_001267550.2:c.25481G>AMANE SELECT
NM_003319.4:c.13282+20829G>A
NM_133378.4:c.21749G>A
NM_133432.3:c.13657+20829G>A
NM_133437.4:c.13858+20829G>A
NP_001243779.1:p.Arg8177Gln
NP_001254479.2:p.Arg8494Gln
NP_596869.4:p.Arg7250Gln
LRG_391:g.118550G>A
NC_000002.11:g.179581980C>T

Protein change:

R7250Q

Links:

dbSNP: rs201418615

NCBI 1000 Genomes Browser:

rs201418615

Molecular consequence:

NM_003319.4:c.13282+20829G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_133432.3:c.13657+20829G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_133437.4:c.13858+20829G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_001256850.1:c.24530G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.25481G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.21749G>A - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000055047	Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq	criteria provided, single submitter (Ng et al. (Circ Cardiovasc Genet. 2013))	Likely benign (Jun 24, 2013)	unknown	research	PubMed (1) [See all records that cite this PMID]
SCV000232857	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Uncertain significance (Aug 29, 2014)	germline	clinical testing	Citation Link,
SCV000714643	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely benign (Oct 7, 2020)	germline	clinical testing	Citation Link,
SCV001919643	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	Likely benign	germline	clinical testing
SCV001966755	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	Likely benign	germline	clinical testing
SCV003824797	Revvity Omics, Revvity	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely benign (Aug 17, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

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Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	2	not provided	not provided	not provided	not provided	clinical testing
not provided	unknown	unknown	2	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

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

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Biesecker Lab/Clinical Genomics Section, National Institutes of Health - ClinSeq, SCV000055047.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	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		2	not provided	not provided	not provided

From Eurofins Ntd Llc (ga), SCV000232857.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	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		2	not provided	not provided	not provided

From GeneDx, SCV000714643.2

#	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 associated with the following publications: (PMID: 27604489, 23861362)

#	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, Academic Medical Center - VKGL Data-share Consensus, SCV001919643.1

#	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, SCV001966755.1

#	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 Revvity Omics, Revvity, SCV003824797.2

#	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

Last Updated: Sep 29, 2024

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