NM_001267550.2(TTN):c.107840T>A (p.Ile35947Asn) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Jul 1, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001319595.1

Allele description [Variation Report for NM_001267550.2(TTN):c.107840T>A (p.Ile35947Asn)]

NM_001267550.2(TTN):c.107840T>A (p.Ile35947Asn)

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.107840T>A (p.Ile35947Asn)
HGVS:
  • NC_000002.12:g.178527148A>T
  • NG_011618.3:g.308655T>A
  • NG_051363.1:g.9322A>T
  • NM_001256850.1:c.102917T>A
  • NM_001267550.2:c.107840T>AMANE SELECT
  • NM_003319.4:c.80645T>A
  • NM_133378.4:c.100136T>A
  • NM_133432.3:c.81020T>A
  • NM_133437.4:c.81221T>A
  • NP_001243779.1:p.Ile34306Asn
  • NP_001254479.2:p.Ile35947Asn
  • NP_003310.4:p.Ile26882Asn
  • NP_596869.4:p.Ile33379Asn
  • NP_597676.3:p.Ile27007Asn
  • NP_597681.4:p.Ile27074Asn
  • LRG_391t1:c.107840T>A
  • LRG_391:g.308655T>A
  • LRG_391p1:p.Ile35947Asn
  • NC_000002.11:g.179391875A>T
Nucleotide change:
293329T-A
Protein change:
I26882N
Links:
OMIM: 188840.0006; dbSNP: rs281864928
NCBI 1000 Genomes Browser:
rs281864928
Molecular consequence:
  • NM_001256850.1:c.102917T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.107840T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.80645T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.100136T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.81020T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.81221T>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:
Limb-girdle muscular dystrophy, type 2J (LGMDR10)
Synonyms:
MUSCULAR DYSTROPHY, LIMB-GIRDLE, AUTOSOMAL RECESSIVE 10
Identifiers:
MONDO: MONDO:0012127; MedGen: C1837342; Orphanet: 140922; OMIM: 608807

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001510348Invitaecriteria provided, single submitter
Uncertain significance
(Jul 1, 2020)
germlineclinical testing

PubMed (5)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Tibial muscular dystrophy in a Belgian family.

Van den Bergh PY, Bouquiaux O, Verellen C, Marchand S, Richard I, Hackman P, Udd B.

Ann Neurol. 2003 Aug;54(2):248-51.

PubMed [citation]
PMID:
12891679

Targeted Next-Generation Sequencing Reveals Novel TTN Mutations Causing Recessive Distal Titinopathy.

Evilä A, Palmio J, Vihola A, Savarese M, Tasca G, Penttilä S, Lehtinen S, Jonson PH, De Bleecker J, Rainer P, Auer-Grumbach M, Pouget J, Salort-Campana E, Vilchez JJ, Muelas N, Olive M, Hackman P, Udd B.

Mol Neurobiol. 2017 Nov;54(9):7212-7223. doi: 10.1007/s12035-016-0242-3. Epub 2016 Oct 29.

PubMed [citation]
PMID:
27796757
See all PubMed Citations (5)

Details of each submission

From Invitae, SCV001510348.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (5)

Description

This sequence change replaces isoleucine with asparagine at codon 35947 of the TTN protein (p.Ile35947Asn). There is a large physicochemical difference between isoleucine and asparagine. This variant is present in population databases (rs281864928, ExAC 0.002%). This variant has been observed in individual(s) with clinical features of tibial muscular dystrophy (PMID: 12891679, 27796757). It has also been observed to segregate with disease in related individuals. This variant is also described as ATT>AAT change at position 293,329 in Mex6, I57N, p.I34306N, or p.I33379N in the literature. ClinVar contains an entry for this variant (Variation ID: 12654). This variant is located in the M band of TTN (PMID: 25589632). Variants in this region may be relevant for neuromuscular disorders, but have not been definitively shown to cause cardiomyopathy (PMID: 23975875). This variant has been reported not to substantially affect TTN protein function (PMID: 25877298 25739468). 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Oct 16, 2021

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