rs757119133
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.14152A>G(p.Lys4718Glu) variant causes a missense change. The variant allele was found at a frequency of 0.0000514 in 1,613,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts 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. K4718R) has been classified as Uncertain significance.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.14152A>G | p.Lys4718Glu | missense_variant | 49/363 | ENST00000589042.5 | |
LOC124906101 | XR_007087319.1 | n.673T>C | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.14152A>G | p.Lys4718Glu | missense_variant | 49/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.1133+8T>C | splice_region_variant, intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152216Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000201 AC: 5AN: 248294Hom.: 0 AF XY: 0.0000223 AC XY: 3AN XY: 134706
GnomAD4 exome AF: 0.0000541 AC: 79AN: 1461250Hom.: 0 Cov.: 31 AF XY: 0.0000426 AC XY: 31AN XY: 726890
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152216Hom.: 0 Cov.: 32 AF XY: 0.0000134 AC XY: 1AN XY: 74360
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 | Dec 04, 2017 | - - |
Hypertrophic cardiomyopathy 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | KardioGenetik, Herz- und Diabeteszentrum NRW | May 31, 2023 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 12, 2018 | The p.K4355E variant (also known as c.13063A>G), located in coding exon 45 of the TTN gene, results from an A to G substitution at nucleotide position 13063. The lysine at codon 4355 is replaced by glutamic acid, an amino acid with similar properties. This variant (reported as p.Lys4401Glu, c.13201A>G) was reported to co-occur with a TTN frameshift alteration in an individual with peripartum cardiomyopathy (van Spaendonck-Zwarts KY et al. Eur. Heart J., 2014 Aug;35:2165-73). This amino acid position is well 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. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 10, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at