NM_001267550.2(TTN):c.89989T>A (p.Leu29997Met) AND not specified

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: May 29, 2021
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:: RCV000155823.12

Allele description [Variation Report for NM_001267550.2(TTN):c.89989T>A (p.Leu29997Met)]

NM_001267550.2(TTN):c.89989T>A (p.Leu29997Met)

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.89989T>A (p.Leu29997Met)

Other names:

p.L28356M:TTG>ATG

HGVS:

NC_000002.12:g.178552911A>T
NG_011618.3:g.282892T>A
NG_051363.1:g.35085A>T
NM_001256850.1:c.85066T>A
NM_001267550.2:c.89989T>AMANE SELECT
NM_003319.4:c.62794T>A
NM_133378.4:c.82285T>A
NM_133432.3:c.63169T>A
NM_133437.4:c.63370T>A
NP_001243779.1:p.Leu28356Met
NP_001254479.2:p.Leu29997Met
NP_003310.4:p.Leu20932Met
NP_596869.4:p.Leu27429Met
NP_597676.3:p.Leu21057Met
NP_597681.4:p.Leu21124Met
LRG_391:g.282892T>A
NC_000002.11:g.179417638A>T
NM_003319.4:c.62794T>A

Protein change:

L20932M

Links:

dbSNP: rs369855092

NCBI 1000 Genomes Browser:

rs369855092

Molecular consequence:

NM_001256850.1:c.85066T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.89989T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.62794T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.82285T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.63169T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.63370T>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
SCV000205534	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Benign (Aug 4, 2016)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23396983, 24033266
SCV000237722	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Mar 25, 2016)	germline	clinical testing	Citation Link,
SCV000334934	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Benign (Sep 3, 2015)	germline	clinical testing	Citation Link,
SCV001737867	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (May 29, 2021)	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	not provided	2	2	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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Genetic complexity in hypertrophic cardiomyopathy revealed by high-throughput sequencing.

Lopes LR, Zekavati A, Syrris P, Hubank M, Giambartolomei C, Dalageorgou C, Jenkins S, McKenna W; Uk10k Consortium, Plagnol V, Elliott PM.

J Med Genet. 2013 Apr;50(4):228-39. doi: 10.1136/jmedgenet-2012-101270. Epub 2013 Feb 8.

PubMed [citation]

PMID:: 23396983
PMCID:: PMC3607113

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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000205534.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	2	not provided	not provided	clinical testing	PubMed (2)

Description

p.Leu27429Met in exon 284 of TTN: This variant is not expected to have clinical significance because it is not located within the splice consensus sequence. It has been identified in 1.1% (178/16496) of South Asian chromosomes, including 2 homozygotes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org; dbSNP rs369855092).

#	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		2	not provided	2	not provided

From GeneDx, SCV000237722.6

#	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), SCV000334934.3

#	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, SCV001737867.1

#	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: Oct 20, 2024

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