chr2-178802225-C-T
Variant summary
Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP6
The NM_001267550.2(TTN):c.208G>A(p.Val70Met) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,614,032 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V70V) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
Publications
- dilated cardiomyopathyInheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
- dilated cardiomyopathy 1GInheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
- early-onset myopathy with fatal cardiomyopathyInheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P
- TTN-related myopathyInheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
- myopathy, myofibrillar, 9, with early respiratory failureInheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Ambry Genetics
- tibial muscular dystrophyInheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), ClinGen, Orphanet
- autosomal recessive limb-girdle muscular dystrophy type 2JInheritance: AR Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
- hypertrophic cardiomyopathy 9Inheritance: AD Classification: MODERATE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), PanelApp Australia
- familial isolated dilated cardiomyopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- autosomal recessive centronuclear myopathyInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- childhood-onset progressive contractures-limb-girdle weakness-muscle dystrophy syndromeInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- arrhythmogenic right ventricular cardiomyopathyInheritance: AD Classification: LIMITED Submitted by: ClinGen
- congenital myopathyInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
- hereditary skeletal muscle disorderInheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
- hypertrophic cardiomyopathyInheritance: AD Classification: LIMITED Submitted by: ClinGen
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ACMG classification
Our verdict: Likely_benign. The variant received -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.208G>A | p.Val70Met | missense_variant | Exon 3 of 363 | ENST00000589042.5 | NP_001254479.2 | |
TTN | NM_133379.5 | c.208G>A | p.Val70Met | missense_variant | Exon 3 of 46 | ENST00000360870.10 | NP_596870.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.208G>A | p.Val70Met | missense_variant | Exon 3 of 363 | 5 | NM_001267550.2 | ENSP00000467141.1 | ||
TTN | ENST00000360870.10 | c.208G>A | p.Val70Met | missense_variant | Exon 3 of 46 | 5 | NM_133379.5 | ENSP00000354117.4 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152174Hom.: 0 Cov.: 32 show subpopulations
GnomAD2 exomes AF: 0.0000477 AC: 12AN: 251358 AF XY: 0.0000736 show subpopulations
GnomAD4 exome AF: 0.0000219 AC: 32AN: 1461858Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20AN XY: 727238 show subpopulations
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152174Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74334 show subpopulations
ClinVar
Submissions by phenotype
not provided Uncertain:2
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Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
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Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at