rs727503551
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001267550.2(TTN):c.87805G>A(p.Val29269Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,960 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. V29269V) has been classified as Likely benign.
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.87805G>A | p.Val29269Ile | missense_variant | 329/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2043+15096C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.87805G>A | p.Val29269Ile | missense_variant | 329/363 | 5 | NM_001267550.2 | P1 | |
ENST00000624360.1 | n.2897C>T | non_coding_transcript_exon_variant | 1/1 | ||||||
TTN-AS1 | ENST00000659121.1 | n.416+33821C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000328 AC: 5AN: 152214Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000322 AC: 8AN: 248732Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134922
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461628Hom.: 0 Cov.: 33 AF XY: 0.0000358 AC XY: 26AN XY: 727090
GnomAD4 genome AF: 0.0000328 AC: 5AN: 152332Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74490
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 01, 2018 | 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. - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Uncertain significance, no assertion criteria provided | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 11, 2019 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 15, 2013 | The Val26701Ile variant in TTN has not been reported in individuals with cardiom yopathy or in large population studies. Computational analyses (biochemical amin o acid properties, conservation, AlignGVGD, PolyPhen2, and SIFT) do not provide strong support for or against an impact to the protein. Additional information i s needed to fully assess the clinical significance of the Val26701Ile variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at