2-178776400-T-G
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_001267550.2(TTN):c.5464A>C(p.Met1822Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00025 in 1,612,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.5464A>C | p.Met1822Leu | missense_variant | 28/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.5464A>C | p.Met1822Leu | missense_variant | 28/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.5464A>C | p.Met1822Leu | missense_variant | 28/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.5464A>C | p.Met1822Leu | missense_variant | 28/46 | 5 | NM_133379.5 | ||
TTN-AS1 | ENST00000659121.1 | n.3827T>G | non_coding_transcript_exon_variant | 12/13 |
Frequencies
GnomAD3 genomes ? AF: 0.000184 AC: 28AN: 152184Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000280 AC: 70AN: 250038Hom.: 0 AF XY: 0.000355 AC XY: 48AN XY: 135248
GnomAD4 exome AF: 0.000257 AC: 375AN: 1459876Hom.: 0 Cov.: 33 AF XY: 0.000244 AC XY: 177AN XY: 726358
GnomAD4 genome ? AF: 0.000184 AC: 28AN: 152184Hom.: 0 Cov.: 33 AF XY: 0.000202 AC XY: 15AN XY: 74356
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 30, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Apr 25, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 23, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Apr 06, 2017 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Cardiovascular phenotype Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 15, 2019 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at