NM_001267550.2(TTN):c.72001G>A (p.Ala24001Thr) AND not specified

Clinical significance:Likely benign (Last evaluated: Oct 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:
RCV000184164.4

Allele description [Variation Report for NM_001267550.2(TTN):c.72001G>A (p.Ala24001Thr)]

NM_001267550.2(TTN):c.72001G>A (p.Ala24001Thr)

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.72001G>A (p.Ala24001Thr)
Other names:
p.A21433T:GCC>ACC
HGVS:
  • NC_000002.12:g.178574131C>T
  • NG_011618.3:g.261672G>A
  • NG_051363.1:g.56305C>T
  • NM_001256850.1:c.67078G>A
  • NM_001256850.1:c.67078G>A
  • NM_001267550.2:c.72001G>AMANE SELECT
  • NM_001267550.2:c.72001G>AMANE SELECT
  • NM_003319.4:c.44806G>A
  • NM_133378.4:c.64297G>A
  • NM_133378.4:c.64297G>A
  • NM_133432.3:c.45181G>A
  • NM_133437.4:c.45382G>A
  • NP_001243779.1:p.Ala22360Thr
  • NP_001243779.1:p.Ala22360Thr
  • NP_001254479.2:p.Ala24001Thr
  • NP_001254479.2:p.Ala24001Thr
  • NP_003310.4:p.Ala14936Thr
  • NP_596869.4:p.Ala21433Thr
  • NP_596869.4:p.Ala21433Thr
  • NP_597676.3:p.Ala15061Thr
  • NP_597681.4:p.Ala15128Thr
  • LRG_391:g.261672G>A
  • NC_000002.11:g.179438858C>T
  • NC_000002.11:g.179438858C>T
  • NM_133379.3:c.*171454G>A
Protein change:
A14936T
Links:
dbSNP: rs180828370
NCBI 1000 Genomes Browser:
rs180828370
Molecular consequence:
  • NM_001256850.1:c.67078G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001267550.2:c.72001G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003319.4:c.44806G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133378.4:c.64297G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133432.3:c.45181G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_133437.4:c.45382G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001442595Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Oct 1, 2020)
germlineclinical testing

Citation Link

Summary from all submissions

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

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001442595.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Variant summary: TTN c.64297G>A (p.Ala21433Thr) results in a non-conservative amino acid change located in the A-band domain of the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00018 in 279544 control chromosomes, predominantly at a frequency of 0.001 within the Latino subpopulation in the gnomAD database. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in TTN causing Dilated Cardiomyopathy phenotype (0.00039), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. To our knowledge, no occurrence of c.64297G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (1x) and likely benign (2x). Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Nov 20, 2021

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