NM_001267550.2(TTN):c.44323G>A (p.Val14775Met) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Sep 28, 2017)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000694203.1

Allele description [Variation Report for NM_001267550.2(TTN):c.44323G>A (p.Val14775Met)]

NM_001267550.2(TTN):c.44323G>A (p.Val14775Met)

Gene:
TTN:titin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q31.2
Genomic location:
Preferred name:
NM_001267550.2(TTN):c.44323G>A (p.Val14775Met)
HGVS:
  • NC_000002.12:g.178629402C>T
  • NG_011618.3:g.206401G>A
  • NM_001256850.1:c.39400G>A
  • NM_001267550.2:c.44323G>AMANE SELECT
  • NM_003319.4:c.17128G>A
  • NM_133378.4:c.36619G>A
  • NM_133432.3:c.17503G>A
  • NM_133437.4:c.17704G>A
  • NP_001243779.1:p.Val13134Met
  • NP_001254479.2:p.Val14775Met
  • NP_003310.4:p.Val5710Met
  • NP_596869.4:p.Val12207Met
  • NP_597676.3:p.Val5835Met
  • NP_597681.4:p.Val5902Met
  • LRG_391t1:c.44323G>A
  • LRG_391:g.206401G>A
  • NC_000002.11:g.179494129C>T
  • NM_001267550.1:c.44323G>A
Protein change:
V12207M
Links:
dbSNP: rs540115992
NCBI 1000 Genomes Browser:
rs540115992
Molecular consequence:
  • NM_001256850.1:c.39400G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.44323G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.17128G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.36619G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.17503G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.17704G>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
SCV000822636Invitaecriteria provided, single submitter
Uncertain significance
(Sep 28, 2017)
germlineclinical testing

PubMed (1)
[See all records that cite this PMID]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000822636.1

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

Description

This sequence change replaces valine with methionine at codon 14775 of the TTN protein (p.Val14775Met). The valine residue is conserved and there is a small physicochemical difference between valine and methionine. This variant is present in population databases (rs540115992, ExAC 0.08%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with TTN-related disease. 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: Apr 12, 2021

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