2-178593412-G-A
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):c.58796C>T(p.Thr19599Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000279 in 1,613,160 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. T19599T) has been classified as Likely benign.
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.58796C>T | p.Thr19599Ile | missense_variant | 299/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.3364+2098G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.58796C>T | p.Thr19599Ile | missense_variant | 299/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-4184G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000171 AC: 26AN: 152036Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000402 AC: 10AN: 248500Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 134840
GnomAD4 exome AF: 0.0000130 AC: 19AN: 1461124Hom.: 0 Cov.: 35 AF XY: 0.00000825 AC XY: 6AN XY: 726844
GnomAD4 genome AF: 0.000171 AC: 26AN: 152036Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74240
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 10, 2020 | This variant is associated with the following publications: (PMID: 31983221) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 27, 2020 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 11, 2017 | The p.Thr17031Ile variant in TTN has been identified by our laboratory in 1 Afri can American individual with DCM. It has also been identified in 11/23996 of Afr ican chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broad institute.org; dbSNP rs367816473). This variant has also been reported in ClinVa r (Variation ID:178204). Computational prediction tools and conservation analysi s do not provide strong support for or against an impact to the protein, though several reptiles and some fish species carry an isoleucine (Ile) at this positio n which suggests that this change may be tolerated. In summary, the clinical sig nificance of the p.Thr17031Ile variant is uncertain. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 04, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at