rs397517778
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 1P and 12B. PP2BP4_StrongBP6_Very_Strong
The NM_001267550.2(TTN):āc.99102G>Cā(p.Trp33034Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000607 in 1,613,730 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. W33034S) has been classified as Uncertain significance.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -11 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.99102G>C | p.Trp33034Cys | missense_variant | 354/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.677C>G | non_coding_transcript_exon_variant | 5/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.99102G>C | p.Trp33034Cys | missense_variant | 354/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.416+15091C>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000789 AC: 12AN: 152120Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000265 AC: 66AN: 248992Hom.: 1 AF XY: 0.000303 AC XY: 41AN XY: 135092
GnomAD4 exome AF: 0.0000588 AC: 86AN: 1461492Hom.: 1 Cov.: 32 AF XY: 0.0000578 AC XY: 42AN XY: 727024
GnomAD4 genome ? AF: 0.0000788 AC: 12AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74440
ClinVar
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 19, 2015 | p.Trp30466Cys in exon 303 of TTN: This variant is not expected to have clinical significance because it has been identified in 0.3% (25/8738) of East Asian chr omosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.o rg; dbSNP rs397517778). - |
Likely benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 17, 2017 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 16, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 23, 2019 | This variant is associated with the following publications: (PMID: 23861362) - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 27, 2019 | 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