NM_001267550.2(TTN):c.106876T>G (p.Leu35626Val) AND not specified

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 30, 2014
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV000154868.4

Allele description [Variation Report for NM_001267550.2(TTN):c.106876T>G (p.Leu35626Val)]

NM_001267550.2(TTN):c.106876T>G (p.Leu35626Val)

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.106876T>G (p.Leu35626Val)

HGVS:

NC_000002.12:g.178528875A>C
NG_011618.3:g.306928T>G
NG_051363.1:g.11049A>C
NM_001256850.1:c.101953T>G
NM_001267550.2:c.106876T>GMANE SELECT
NM_003319.4:c.79681T>G
NM_133378.4:c.99172T>G
NM_133432.3:c.80056T>G
NM_133437.4:c.80257T>G
NP_001243779.1:p.Leu33985Val
NP_001254479.2:p.Leu35626Val
NP_003310.4:p.Leu26561Val
NP_596869.4:p.Leu33058Val
NP_597676.3:p.Leu26686Val
NP_597681.4:p.Leu26753Val
LRG_391:g.306928T>G
NC_000002.11:g.179393602A>C
NM_001267550.2:c.106876T>G
NM_003319.4:c.79681T>G

Protein change:

L26561V

Links:

dbSNP: rs373152640

NCBI 1000 Genomes Browser:

rs373152640

Molecular consequence:

NM_001256850.1:c.101953T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.106876T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.79681T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.99172T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.80056T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.80257T>G - 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
SCV000204550	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Uncertain significance (Jun 30, 2014)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000204550

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

criteria provided, single submitter

(LMM Criteria)

Uncertain significance
(Jun 30, 2014)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	1	1	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 Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine, SCV000204550.5

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

Description

Variant classified as Uncertain Significance - Favor Benign. The Leu33058Val var iant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/8330 European American chromosomes by the NHLBI Ex ome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs373152640). C omputational prediction tools and conservation analysis do not provide strong su pport for or against an impact to the protein, though 2 birds and 4 reptiles hav e a valine (Val) at this position, suggesting that this change may be tolerated. In summary, the clinical significance of the Leu33058Val variant is uncertain, though the presence of this variant in other species suggests that it is more li kely to be benign.

#	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

Last Updated: Jan 13, 2025

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