rs762136167
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):c.105182C>T(p.Ala35061Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000167 in 1,613,754 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 Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A35061E) 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 Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.105182C>T | p.Ala35061Val | missense_variant | 358/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.220-4299G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.105182C>T | p.Ala35061Val | missense_variant | 358/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.416+7797G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000281 AC: 7AN: 248976Hom.: 0 AF XY: 0.0000296 AC XY: 4AN XY: 135072
GnomAD4 exome AF: 0.0000157 AC: 23AN: 1461604Hom.: 0 Cov.: 41 AF XY: 0.0000179 AC XY: 13AN XY: 727106
GnomAD4 genome ? AF: 0.0000263 AC: 4AN: 152150Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74312
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | May 25, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Aug 29, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 25, 2020 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Sep 06, 2019 | The p.A25996V variant (also known as c.77987C>T), located in coding exon 185 of the TTN gene, results from a C to T substitution at nucleotide position 77987. The alanine at codon 25996 is replaced by valine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species, and valine 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at