chr2-178767796-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.9434G>A(p.Arg3145Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000198 in 1,614,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 11/18 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 | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.9434G>A | p.Arg3145Lys | missense_variant | 40/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.9434G>A | p.Arg3145Lys | missense_variant | 40/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.9434G>A | p.Arg3145Lys | missense_variant | 40/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.9434G>A | p.Arg3145Lys | missense_variant | 40/46 | 5 | NM_133379.5 | ||
TTN-AS1 | ENST00000659121.1 | n.1592+3428C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000398 AC: 10AN: 251054Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135664
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461836Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 727224
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74368
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 | Sep 22, 2020 | The p.Arg3145Lys variant in TTN is classified as likely benign because it has been identified in 0.026% (8/30614) of South Asian chromosomes by gnomAD (http://gnomad.broadinstitute.org). Computational prediction tools and conservation analyses do not provide strong support for or against an impact to the protein. ACMG/AMP Criteria applied: BS1. - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 06, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 10, 2020 | The p.R3099K variant (also known as c.9296G>A), located in coding exon 38 of the TTN gene, results from a G to A substitution at nucleotide position 9296. The arginine at codon 3099 is replaced by lysine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at