rs369544339
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_001267550.2(TTN):āc.18663A>Cā(p.Glu6221Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000112 in 1,613,638 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E6221G) has been classified as Uncertain significance.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.18663A>C | p.Glu6221Asp | missense_variant | 64/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.18663A>C | p.Glu6221Asp | missense_variant | 64/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-5011T>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000105 AC: 16AN: 152146Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000926 AC: 23AN: 248470Hom.: 0 AF XY: 0.0000965 AC XY: 13AN XY: 134784
GnomAD4 exome AF: 0.000112 AC: 164AN: 1461374Hom.: 0 Cov.: 33 AF XY: 0.000114 AC XY: 83AN XY: 726970
GnomAD4 genome ? AF: 0.000105 AC: 16AN: 152264Hom.: 0 Cov.: 33 AF XY: 0.0000940 AC XY: 7AN XY: 74456
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 28, 2015 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 11, 2019 | This variant is associated with the following publications: (PMID: 24503780) - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2019 | - - |
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 20, 2015 | The p.Glu4977Asp variant in TTN has been previously identified by our laboratory in 1 Caucasian child with DCM and 1 Caucasian adult with ARVC. This variant has also been identified in 11/67530 European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs369544339). Computatio nal prediction tools and conservation analysis suggest the p.Glu4977Asp variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Glu4977As p variant is uncertain. - |
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | Sep 27, 2019 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 20, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at