2-178730712-T-C
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):āc.17821A>Gā(p.Ile5941Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000192 in 1,613,654 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.17821A>G | p.Ile5941Val | missense_variant | 61/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.17821A>G | p.Ile5941Val | missense_variant | 61/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-3792T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152182Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000324 AC: 8AN: 247102Hom.: 0 AF XY: 0.0000373 AC XY: 5AN XY: 133988
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461354Hom.: 0 Cov.: 40 AF XY: 0.0000151 AC XY: 11AN XY: 726950
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152300Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74468
ClinVar
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Dec 15, 2021 | Variant summary: TTN c.14089A>G (p.Ile4697Val) results in a conservative amino acid change located in the I-band domain of the encoded protein sequence. Two of three in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 3.2e-05 in 247102 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.14089A>G has been reported in the literature in an individual affected with Dilated Cardiomyopathy without strong evidence for causality (Aknrinade_2015). This report does not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 22, 2012 | The Ile4697Val variant in TTN has not been reported in the literature nor previo usly identified by our laboratory. Computational analyses (biochemical amino aci d properties, conservation, AlignGVGD, and SIFT) suggest that this variant may n ot impact to the protein, though this information is not predictive enough to ru le out pathogenicity. Additional information is needed to fully assess the clini cal significance of the Ile5697Val variant. - |
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 16, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 24, 2020 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at