rs367854582
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_001267550.2(TTN):c.21721G>A(p.Val7241Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,392 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).
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.21721G>A | p.Val7241Ile | missense_variant | 75/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.21721G>A | p.Val7241Ile | missense_variant | 75/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-11218C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000191 AC: 29AN: 152120Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000405 AC: 10AN: 246894Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 133950
GnomAD4 exome AF: 0.0000185 AC: 27AN: 1461154Hom.: 0 Cov.: 33 AF XY: 0.0000193 AC XY: 14AN XY: 726838
GnomAD4 genome ? AF: 0.000190 AC: 29AN: 152238Hom.: 0 Cov.: 33 AF XY: 0.000175 AC XY: 13AN XY: 74434
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 06, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 25, 2016 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Feb 12, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | May 22, 2017 | Variant classified as Uncertain Significance - Favor Benign. The p.Val5997Ile va riant in TTN has not been previously reported in individuals with cardiomyopathy , but has been identified in 0.06% (15/23956) of African chromosomes by the geno me Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSNP rs3678 54582). Computational prediction tools and conservation analysis suggest that th e p.Val5997Ile variant may not impact the protein, though this information is no t predictive enough to rule out pathogenicity. In summary, while the clinical si gnificance of the p.Val5997Ile variant is uncertain, these data suggest that it is more likely to be benign. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at