rs779064962
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):c.7339G>A(p.Val2447Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000403 in 1,613,876 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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 -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.7339G>A | p.Val2447Met | missense_variant | 32/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.7339G>A | p.Val2447Met | missense_variant | 32/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.7339G>A | p.Val2447Met | missense_variant | 32/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.7339G>A | p.Val2447Met | missense_variant | 32/46 | 5 | NM_133379.5 | ||
TTN-AS1 | ENST00000659121.1 | n.1653+382C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152120Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000240 AC: 6AN: 250384Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135480
GnomAD4 exome AF: 0.0000335 AC: 49AN: 1461756Hom.: 0 Cov.: 33 AF XY: 0.0000289 AC XY: 21AN XY: 727184
GnomAD4 genome AF: 0.000105 AC: 16AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.0000808 AC XY: 6AN XY: 74298
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 16, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 20, 2020 | - - |
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 14, 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. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 17, 2020 | Variant summary: TTN c.7339G>A (p.Val2447Met) results in a conservative amino acid change located in the I-band region of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 2.4e-05 in 250384 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.71842G>A in individuals affected with Dilated Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=2) or likely benign (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 15, 2016 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 09, 2020 | The p.V2401M variant (also known as c.7201G>A), located in coding exon 30 of the TTN gene, results from a G to A substitution at nucleotide position 7201. The valine at codon 2401 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is not 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. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at