chr2-178746825-C-T
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_133379.5(TTN):c.15575G>A(p.Arg5192Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00041 in 1,613,366 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 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_133379.5 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_133379.5 | c.15575G>A | p.Arg5192Lys | missense_variant | 46/46 | ENST00000360870.10 | |
TTN | NM_001267550.2 | c.11312-4904G>A | intron_variant | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000360870.10 | c.15575G>A | p.Arg5192Lys | missense_variant | 46/46 | 5 | NM_133379.5 | ||
TTN | ENST00000589042.5 | c.11312-4904G>A | intron_variant | 5 | NM_001267550.2 | P1 | |||
TTN-AS1 | ENST00000659121.1 | n.1223+3855C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000329 AC: 50AN: 151920Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000243 AC: 61AN: 250688Hom.: 0 AF XY: 0.000236 AC XY: 32AN XY: 135494
GnomAD4 exome AF: 0.000419 AC: 612AN: 1461328Hom.: 1 Cov.: 33 AF XY: 0.000352 AC XY: 256AN XY: 726986
GnomAD4 genome AF: 0.000329 AC: 50AN: 152038Hom.: 0 Cov.: 32 AF XY: 0.000350 AC XY: 26AN XY: 74324
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:3
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 30, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | TTN: PM2, BP4 - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, University Medical Center Utrecht | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 15, 2018 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 05, 2014 | The Arg5192Lys variant in TTN has not been previously reported in individuals wi th cardiomyopathy, but has been identified in 4/8596 European American chromosom es by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbS NP rs62179016). Computational prediction tools and conservation analysis are lim ited or unavailable for this variant. In summary, the clinical significance of t he Arg5192Lys variant is uncertain. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at