rs371056974
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_ModerateBP6
The NM_001267550.2(TTN):c.919G>A(p.Val307Met) variant causes a missense change. The variant allele was found at a frequency of 0.0000266 in 1,613,936 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V307V) 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.919G>A | p.Val307Met | missense_variant | Exon 7 of 363 | ENST00000589042.5 | NP_001254479.2 | |
TTN | NM_133379.5 | c.919G>A | p.Val307Met | missense_variant | Exon 7 of 46 | ENST00000360870.10 | NP_596870.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.919G>A | p.Val307Met | missense_variant | Exon 7 of 363 | 5 | NM_001267550.2 | ENSP00000467141.1 | ||
TTN | ENST00000360870.10 | c.919G>A | p.Val307Met | missense_variant | Exon 7 of 46 | 5 | NM_133379.5 | ENSP00000354117.4 |
Frequencies
GnomAD3 genomes AF: 0.0000592 AC: 9AN: 151996Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000478 AC: 12AN: 250840 AF XY: 0.0000516 show subpopulations
GnomAD4 exome AF: 0.0000233 AC: 34AN: 1461824Hom.: 0 Cov.: 32 AF XY: 0.0000275 AC XY: 20AN XY: 727216 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.0000592 AC: 9AN: 152112Hom.: 0 Cov.: 33 AF XY: 0.0000672 AC XY: 5AN XY: 74394 show subpopulations
Age Distribution
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
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Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at