rs367816473
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).
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 | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.58796C>T | p.Thr19599Ile | missense_variant | 299/363 | ENST00000589042.5 | NP_001254479.2 | |
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 | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.58796C>T | p.Thr19599Ile | missense_variant | 299/363 | 5 | NM_001267550.2 | ENSP00000467141 | 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
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Mar 27, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 10, 2020 | This variant is associated with the following publications: (PMID: 31983221) - |
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 | Labcorp Genetics (formerly Invitae), Labcorp | Aug 04, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at