NM_001267550.2(TTN):c.67495C>T (p.Arg22499Ter) AND multiple conditions

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Oct 9, 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:: RCV000680139.3

Allele description [Variation Report for NM_001267550.2(TTN):c.67495C>T (p.Arg22499Ter)]

NM_001267550.2(TTN):c.67495C>T (p.Arg22499Ter)

Genes:

LOC126806423:CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:179443309-179444508 [Gene]
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.67495C>T (p.Arg22499Ter)

HGVS:

NC_000002.12:g.178579702G>A
NG_011618.3:g.256101C>T
NG_051363.1:g.61876G>A
NM_001256850.1:c.62572C>T
NM_001267550.2:c.67495C>TMANE SELECT
NM_003319.4:c.40300C>T
NM_133378.4:c.59791C>T
NM_133432.3:c.40675C>T
NM_133437.4:c.40876C>T
NP_001243779.1:p.Arg20858Ter
NP_001254479.2:p.Arg22499Ter
NP_003310.4:p.Arg13434Ter
NP_596869.4:p.Arg19931Ter
NP_597676.3:p.Arg13559Ter
NP_597681.4:p.Arg13626Ter
LRG_391t1:c.67495C>T
LRG_391:g.256101C>T
NC_000002.11:g.179444429G>A
NM_001267550.1:c.67495C>T
NM_003319.4:c.40300C>T

Protein change:

R13434*

Links:

dbSNP: rs574660186

NCBI 1000 Genomes Browser:

rs574660186

Molecular consequence:

NM_001256850.1:c.62572C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001267550.2:c.67495C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_003319.4:c.40300C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_133378.4:c.59791C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_133432.3:c.40675C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_133437.4:c.40876C>T - nonsense - [Sequence Ontology: SO:0001587]

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

Name:: Tibial muscular dystrophy (TMD)
Synonyms:: UDD MYOPATHY; Tibial muscular dystrophy, tardive; Udd Distal Myopathy
Identifiers:: MONDO: MONDO:0010870; MedGen: C1838244; Orphanet: 609; OMIM: 600334

Name:: Myopathy, myofibrillar, 9, with early respiratory failure (MFM9)
Synonyms:: EDSTROM MYOPATHY; MYOPATHY, PROXIMAL, WITH EARLY RESPIRATORY MUSCLE INVOLVEMENT; Myopathy, distal, with early respiratory failure, autosomal dominant
Identifiers:: MONDO: MONDO:0011362; MedGen: C1863599; Orphanet: 178464; Orphanet: 34521; OMIM: 603689

Name:: Early-onset myopathy with fatal cardiomyopathy (CMYO5)
Synonyms:: CONGENITAL MYOPATHY 5 WITH CARDIOMYOPATHY; Salih Myopathy
Identifiers:: MONDO: MONDO:0012714; MedGen: C2673677; Orphanet: 289377; OMIM: 611705

Name:: Hypertrophic cardiomyopathy 9
Synonyms:: Familial hypertrophic cardiomyopathy 9
Identifiers:: MONDO: MONDO:0013412; MedGen: C1861065; OMIM: 613765

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000807583	Baylor Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Sep 1, 2017)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 22335739, 25741868, 25326635
SCV002792378	Fulgent Genetics, Fulgent Genetics	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Oct 9, 2021)	unknown	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

SCV000807583

Baylor Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Sep 1, 2017)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

SCV002792378

Fulgent Genetics, Fulgent Genetics

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Oct 9, 2021)

unknown

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

Citations

PubMed

Truncations of titin causing dilated cardiomyopathy.

Herman DS, Lam L, Taylor MR, Wang L, Teekakirikul P, Christodoulou D, Conner L, DePalma SR, McDonough B, Sparks E, Teodorescu DL, Cirino AL, Banner NR, Pennell DJ, Graw S, Merlo M, Di Lenarda A, Sinagra G, Bos JM, Ackerman MJ, Mitchell RN, Murry CE, et al.

N Engl J Med. 2012 Feb 16;366(7):619-28. doi: 10.1056/NEJMoa1110186.

PubMed [citation]

PMID:: 22335739
PMCID:: PMC3660031

Molecular findings among patients referred for clinical whole-exome sequencing.

Yang Y, Muzny DM, Xia F, Niu Z, Person R, Ding Y, Ward P, Braxton A, Wang M, Buhay C, Veeraraghavan N, Hawes A, Chiang T, Leduc M, Beuten J, Zhang J, He W, Scull J, Willis A, Landsverk M, Craigen WJ, Bekheirnia MR, et al.

JAMA. 2014 Nov 12;312(18):1870-9. doi: 10.1001/jama.2014.14601.

PubMed [citation]

PMID:: 25326635
PMCID:: PMC4326249

See all PubMed Citations (3)

Details of each submission

From Baylor Genetics, SCV000807583.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing (GTR000508680.4)	PubMed (3)

Description

This variant has been previously reported as disease-causing and was found twice in our laboratory: heterozygous (maternally inherited) in a 12-year-old female with dilated cardiomyopathy and paternal family history of dilated cardiomyopathy (who also carried a paternally inherited likely pathogenic variant in BAG3); in trans with a missense variant in a 14-year-old female with global delays, epilepsy, scoliosis, clubbed digits, constipation (who also carried a de novo pathogenic variant in KCNT1).

#	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	(GTR000508680.4)	not provided	not provided	not provided	not provided

From Fulgent Genetics, Fulgent Genetics, SCV002792378.1

#	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	unknown	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: May 16, 2025

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