chr2-178767796-C-T
Variant summary
Our verdict is Likely benign. The variant received -3 ACMG points: 0P and 3B. BP4_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. 12/19 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
Publications
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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.9434G>A | p.Arg3145Lys | missense_variant | Exon 40 of 363 | ENST00000589042.5 | NP_001254479.2 | |
TTN | NM_133379.5 | c.9434G>A | p.Arg3145Lys | missense_variant | Exon 40 of 46 | ENST00000360870.10 | NP_596870.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.9434G>A | p.Arg3145Lys | missense_variant | Exon 40 of 363 | 5 | NM_001267550.2 | ENSP00000467141.1 | ||
TTN | ENST00000360870.10 | c.9434G>A | p.Arg3145Lys | missense_variant | Exon 40 of 46 | 5 | NM_133379.5 | ENSP00000354117.4 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 33 show subpopulations
GnomAD2 exomes AF: 0.0000398 AC: 10AN: 251054 AF XY: 0.0000663 show subpopulations
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461836Hom.: 0 Cov.: 31 AF XY: 0.0000330 AC XY: 24AN XY: 727224 show subpopulations
Age Distribution
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152212Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74368 show subpopulations
ClinVar
Submissions by phenotype
not specified Benign:2
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. -
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
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