NM_001267550.2(TTN):c.6927T>A (p.Asn2309Lys) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 4, 2017
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:: RCV000642748.3

Allele description [Variation Report for NM_001267550.2(TTN):c.6927T>A (p.Asn2309Lys)]

NM_001267550.2(TTN):c.6927T>A (p.Asn2309Lys)

Genes:

LOC126806433:BRD4-independent group 4 enhancer GRCh37_chr2:179638309-179639508 [Gene]
TTN:titin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

2q31.2

Genomic location:

Preferred name:

NM_001267550.2(TTN):c.6927T>A (p.Asn2309Lys)

HGVS:

NC_000002.12:g.178774337A>T
NG_011618.3:g.61466T>A
NM_001256850.1:c.6927T>A
NM_001267550.2:c.6927T>AMANE SELECT
NM_003319.4:c.6789T>A
NM_133378.4:c.6927T>A
NM_133379.5:c.6927T>A
NM_133432.3:c.6789T>A
NM_133437.4:c.6789T>A
NP_001243779.1:p.Asn2309Lys
NP_001254479.2:p.Asn2309Lys
NP_003310.4:p.Asn2263Lys
NP_596869.4:p.Asn2309Lys
NP_596870.2:p.Asn2309Lys
NP_597676.3:p.Asn2263Lys
NP_597681.4:p.Asn2263Lys
LRG_391:g.61466T>A
NC_000002.11:g.179639064A>T
NM_003319.4:c.6789T>A

Protein change:

N2263K

Links:

dbSNP: rs147580120

NCBI 1000 Genomes Browser:

rs147580120

Molecular consequence:

NM_001256850.1:c.6927T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001267550.2:c.6927T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_003319.4:c.6789T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133378.4:c.6927T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133379.5:c.6927T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133432.3:c.6789T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_133437.4:c.6789T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Dilated cardiomyopathy 1G (CMD1G)
Identifiers:: MONDO: MONDO:0011400; MedGen: C1858763; Orphanet: 154; OMIM: 604145

Name:: Autosomal recessive limb-girdle muscular dystrophy type 2J (LGMDR10)
Synonyms:: Limb-girdle muscular dystrophy, type 2J; MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 10
Identifiers:: MONDO: MONDO:0012127; MedGen: C1837342; Orphanet: 140922; OMIM: 608807

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000764435	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 4, 2017)	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

SCV000764435

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 4, 2017)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group, Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000764435.2

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

Description

This sequence change replaces asparagine with lysine at codon 2309 of the TTN protein (p.Asn2309Lys). There is a moderate physicochemical difference between asparagine and lysine. This variant is present in population databases (rs147580120, ExAC 0.07%). This variant has not been reported in the literature in individuals with TTN-related disease. ClinVar contains an entry for this variant (Variation ID: 192073). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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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