NM_001267550.2(TTN):c.107593G>A (p.Glu35865Lys) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Aug 25, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001349766.1

Allele description [Variation Report for NM_001267550.2(TTN):c.107593G>A (p.Glu35865Lys)]

NM_001267550.2(TTN):c.107593G>A (p.Glu35865Lys)

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.107593G>A (p.Glu35865Lys)
HGVS:
  • NC_000002.12:g.178527533C>T
  • NG_011618.3:g.308270G>A
  • NG_051363.1:g.9707C>T
  • NM_001256850.1:c.102670G>A
  • NM_001267550.2:c.107593G>AMANE SELECT
  • NM_003319.4:c.80398G>A
  • NM_133378.4:c.99889G>A
  • NM_133432.3:c.80773G>A
  • NM_133437.4:c.80974G>A
  • NP_001243779.1:p.Glu34224Lys
  • NP_001254479.2:p.Glu35865Lys
  • NP_003310.4:p.Glu26800Lys
  • NP_596869.4:p.Glu33297Lys
  • NP_597676.3:p.Glu26925Lys
  • NP_597681.4:p.Glu26992Lys
  • LRG_391:g.308270G>A
  • NC_000002.11:g.179392260C>T
Protein change:
E26800K
Links:
dbSNP: rs372841288
NCBI 1000 Genomes Browser:
rs372841288
Molecular consequence:
  • NM_001256850.1:c.102670G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.107593G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.80398G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.99889G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.80773G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.80974G>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
SCV001544126Invitaecriteria provided, single submitter
Uncertain significance
(Aug 25, 2020)
germlineclinical testing

PubMed (3)
[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

Integrated allelic, transcriptional, and phenomic dissection of the cardiac effects of titin truncations in health and disease.

Roberts AM, Ware JS, Herman DS, Schafer S, Baksi J, Bick AG, Buchan RJ, Walsh R, John S, Wilkinson S, Mazzarotto F, Felkin LE, Gong S, MacArthur JA, Cunningham F, Flannick J, Gabriel SB, Altshuler DM, Macdonald PS, Heinig M, Keogh AM, Hayward CS, et al.

Sci Transl Med. 2015 Jan 14;7(270):270ra6. doi: 10.1126/scitranslmed.3010134.

PubMed [citation]
PMID:
25589632
PMCID:
PMC4560092

Recessive truncating titin gene, TTN, mutations presenting as centronuclear myopathy.

Ceyhan-Birsoy O, Agrawal PB, Hidalgo C, Schmitz-Abe K, DeChene ET, Swanson LC, Soemedi R, Vasli N, Iannaccone ST, Shieh PB, Shur N, Dennison JM, Lawlor MW, Laporte J, Markianos K, Fairbrother WG, Granzier H, Beggs AH.

Neurology. 2013 Oct 1;81(14):1205-14. doi: 10.1212/WNL.0b013e3182a6ca62. Epub 2013 Aug 23.

PubMed [citation]
PMID:
23975875
PMCID:
PMC3795603
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001544126.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change replaces glutamic acid with lysine at codon 35865 of the TTN protein (p.Glu35865Lys). There is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs372841288, ExAC 0.001%). This variant has not been reported in the literature in individuals with TTN-related conditions. ClinVar contains an entry for this variant (Variation ID: 502239). 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). Algorithms developed to predict the effect of missense changes on protein structure and function are unavailable for the TTN gene. 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 6, 2021

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