rs1422047351
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001267550.2(TTN):c.106556A>G(p.Lys35519Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000739 in 1,352,428 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. K35519K) has been classified as Benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.106556A>G | p.Lys35519Arg | missense_variant | 360/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.219+5559T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.106556A>G | p.Lys35519Arg | missense_variant | 360/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.416+5559T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000728 AC: 1AN: 137420Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 72438
GnomAD4 exome AF: 7.39e-7 AC: 1AN: 1352428Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 662980
GnomAD4 genome ? Cov.: 33
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 | Sep 25, 2017 | This sequence change replaces lysine with arginine at codon 35519 of the TTN protein (p.Lys35519Arg). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and arginine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with TTN-related disease. This variant identified in the TTN gene is located in the M band of the resulting protein (PMID: 25589632). It is unclear how this variant impacts the function of this protein. Algorithms developed to predict the effect of missense changes on protein structure and function are unavailable for the TTN gene. In summary, this variant is a novel missense change with unknown impact on protein function. Missense variants in this region of the TTN gene are typically not causative for cardiac disease, but may be relevant for neuromuscular disorders. However, the available evidence is currently insufficient to determine this variant’s role in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at