rs753036867
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001267550.2(TTN):c.9326A>G(p.Lys3109Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000112 in 1,613,962 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 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.9326A>G | p.Lys3109Arg | missense_variant | 40/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.9326A>G | p.Lys3109Arg | missense_variant | 40/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.9326A>G | p.Lys3109Arg | missense_variant | 40/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.9326A>G | p.Lys3109Arg | missense_variant | 40/46 | 5 | NM_133379.5 | ||
TTN-AS1 | ENST00000659121.1 | n.1592+3536T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000657 AC: 10AN: 152164Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000119 AC: 3AN: 251060Hom.: 0 AF XY: 0.00000737 AC XY: 1AN XY: 135684
GnomAD4 exome AF: 0.00000547 AC: 8AN: 1461798Hom.: 0 Cov.: 31 AF XY: 0.00000413 AC XY: 3AN XY: 727200
GnomAD4 genome ? AF: 0.0000657 AC: 10AN: 152164Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74338
ClinVar
Submissions by phenotype
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 25, 2016 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Oct 07, 2019 | The p.K3063R variant (also known as c.9188A>G), located in coding exon 38 of the TTN gene, results from an A to G substitution at nucleotide position 9188. The lysine at codon 3063 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species; however, arginine is the reference amino acid in other 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. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 17, 2017 | 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at