rs371752190
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_001267550.2(TTN):c.34954G>T(p.Val11652Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000021 in 1,572,426 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 Uncertain significance (★★).
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.34954G>T | p.Val11652Leu | missense_variant | 155/363 | ENST00000589042.5 | NP_001254479.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.34954G>T | p.Val11652Leu | missense_variant | 155/363 | 5 | NM_001267550.2 | ENSP00000467141.1 |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 151836Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000160 AC: 3AN: 187966Hom.: 0 AF XY: 0.00000989 AC XY: 1AN XY: 101122
GnomAD4 exome AF: 0.0000120 AC: 17AN: 1420590Hom.: 0 Cov.: 32 AF XY: 0.0000114 AC XY: 8AN XY: 703684
GnomAD4 genome AF: 0.000105 AC: 16AN: 151836Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74148
ClinVar
Submissions by phenotype
not provided Uncertain:2Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Sep 09, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories | Aug 11, 2020 | The TTN c.34954G>T; p.Val11652Leu variant (rs371752190; ClinVar Variation ID: 202593) is rare in the general population (<0.2% allele frequency in the Genome Aggregation Database) and has not been reported in the medical literature in association with dilated cardiomyopathy (DCM) or other TTN-related disease. The clinical relevance of rare missense variants in this gene, which are identified on average once per individual sequenced in affected populations (Herman 2012), is not well understood. Yet, evidence suggests that the vast majority of such missense variants do not contribute to the clinical outcome of DCM (Begay 2015). Thus, the clinical significance of the p.Val11652Leu variant cannot be determined with certainty. - |
not provided, no classification provided | clinical testing | GeneDx | Jun 20, 2014 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 11, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at