2-178548444-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001267550.2(TTN):c.93182G>A(p.Arg31061His) variant causes a missense change. The variant allele was found at a frequency of 0.0000266 in 1,613,744 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).
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.93182G>A | p.Arg31061His | missense_variant | 339/363 | ENST00000589042.5 | NP_001254479.2 | |
TTN-AS1 | NR_038272.1 | n.2043+6083C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.93182G>A | p.Arg31061His | missense_variant | 339/363 | 5 | NM_001267550.2 | ENSP00000467141 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.416+24808C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000789 AC: 12AN: 152150Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000362 AC: 9AN: 248296Hom.: 0 AF XY: 0.0000297 AC XY: 4AN XY: 134656
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461594Hom.: 0 Cov.: 34 AF XY: 0.0000179 AC XY: 13AN XY: 727082
GnomAD4 genome AF: 0.0000789 AC: 12AN: 152150Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74316
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 17, 2014 | The Arg28493His variant in TTN has not been previously reported in individuals w ith cardiomyopathy or in large population studies. Computational analyses (bioch emical amino acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do n ot provide strong support for or against an impact to the protein. Additional in formation is needed to fully assess the clinical significance of this variant. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 05, 2018 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 10, 2020 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 31, 2020 | 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