NM_001267550.2(TTN):c.85691A>T (p.Lys28564Ile) AND not specified

Germline classification:: Benign/Likely benign (4 submissions)
Last evaluated:: May 7, 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:: RCV000040716.20

Allele description [Variation Report for NM_001267550.2(TTN):c.85691A>T (p.Lys28564Ile)]

NM_001267550.2(TTN):c.85691A>T (p.Lys28564Ile)

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.85691A>T (p.Lys28564Ile)

Other names:

p.K26923I:AAA>ATA

HGVS:

NC_000002.12:g.178560441T>A
NG_011618.3:g.275362A>T
NG_051363.1:g.42615T>A
NM_001256850.1:c.80768A>T
NM_001267550.2:c.85691A>TMANE SELECT
NM_003319.4:c.58496A>T
NM_133378.4:c.77987A>T
NM_133432.3:c.58871A>T
NM_133437.4:c.59072A>T
NP_001243779.1:p.Lys26923Ile
NP_001254479.1:p.Lys28564Ile
NP_001254479.2:p.Lys28564Ile
NP_003310.4:p.Lys19499Ile
NP_596869.4:p.Lys25996Ile
NP_596869.4:p.Lys25996Ile
NP_597676.3:p.Lys19624Ile
NP_597681.4:p.Lys19691Ile
LRG_391t1:c.85691A>T
LRG_391:g.275362A>T
LRG_391p1:p.Lys28564Ile
NC_000002.11:g.179425168T>A
NM_001267550.1:c.85691A>T
NM_003319.4:c.58496A>T
NM_133379.3:c.*185144A>T
c.77987A>T

Protein change:

K19499I

Links:

dbSNP: rs199859344

NCBI 1000 Genomes Browser:

rs199859344

Molecular consequence:

NM_001256850.1:c.80768A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.85691A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.58496A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.77987A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.58871A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.59072A>T - 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
SCV000064407	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	criteria provided, single submitter (LMM Criteria)	Likely benign (Apr 11, 2012)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV000203680	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL Classification Definitions 2015)	Likely benign (Feb 28, 2017)	germline	clinical testing	Citation Link,
SCV000237665	GeneDx	criteria provided, single submitter (GeneDx Variant Classification (06012015))	Benign (Oct 29, 2015)	germline	clinical testing	Citation Link,
SCV002547663	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (May 7, 2022)	germline	clinical testing	Citation Link

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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	3	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	not provided	3	3	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, SCV000064407.6

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

Description

Lys25996Ile in exon 275 of TTN: This variant is not expected to have clinical si gnificance because it has been identified in 0.5% (14/3022) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http: //evs.gs.washington.edu/EVS/) Lys25996Ile in exon 275 of TTN (allele frequenc y = 0.46%, 14/3022) **

#	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		3	not provided	3	not provided

From Eurofins Ntd Llc (ga), SCV000203680.7

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	3	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		3	not provided	not provided	not provided

From GeneDx, SCV000237665.13

#	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 Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV002547663.1

#	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 8, 2024

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