2-178607676-G-A
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_001267550.2(TTN):c.53012C>T(p.Ala17671Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000186 in 1,612,824 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).
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.53012C>T | p.Ala17671Val | missense_variant | 277/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.53012C>T | p.Ala17671Val | missense_variant | 277/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.502+9995G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 151988Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000162 AC: 4AN: 247452Hom.: 0 AF XY: 0.00000745 AC XY: 1AN XY: 134314
GnomAD4 exome AF: 0.00000958 AC: 14AN: 1460718Hom.: 0 Cov.: 32 AF XY: 0.00000550 AC XY: 4AN XY: 726676
GnomAD4 genome AF: 0.000105 AC: 16AN: 152106Hom.: 0 Cov.: 33 AF XY: 0.000121 AC XY: 9AN XY: 74344
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Nov 06, 2017 | Variant classified as Uncertain Significance - Favor Benign. The p.Ala15103Val v ariant in TTN has not been previously reported in individuals with cardiomyopath y, but has been identified in 5/23972 of African chromosomes by the Genome Aggre gation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs549478203). A lanine (Ala) at position 15103 is not conserved in mammals or evolutionarily dis tant species and at least 10 fish species carry a valine (Val) at this position, raising the possibility that a change at this position may be tolerated. Additi onal computational prediction tools suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogeni city. In summary, while the clinical significance of the p.Ala15103Val variant i s uncertain, these data suggest that it is more likely to be benign. ACMG/AMP Cr iteria applied: BP4 (Richards 2015). - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 16, 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. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 12, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Oct 06, 2020 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 30, 2013 | There is insufficient or conflicting evidence for classification of this alteration. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at