rs373527448
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_001267550.2(TTN):c.58190C>T(p.Thr19397Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000397 in 1,613,326 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). Synonymous variant affecting the same amino acid position (i.e. T19397T) 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.58190C>T | p.Thr19397Met | missense_variant | 297/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.3364+2889G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.58190C>T | p.Thr19397Met | missense_variant | 297/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-3393G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000138 AC: 21AN: 152064Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000887 AC: 22AN: 247970Hom.: 0 AF XY: 0.0000743 AC XY: 10AN XY: 134506
GnomAD4 exome AF: 0.0000294 AC: 43AN: 1461144Hom.: 0 Cov.: 34 AF XY: 0.0000234 AC XY: 17AN XY: 726856
GnomAD4 genome ? AF: 0.000138 AC: 21AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74382
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 02, 2014 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 02, 2019 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Aug 07, 2014 | Variant classified as Uncertain Significance - Favor Benign. The Thr16829Met var iant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 1/3818 African American chromosomes by the NHLBI Exo me Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs373527448). Th e threonine (Thr) at position 16829 is not conserved in mammals or evolutionaril y distant species and at least 7 fish species carry a methionine (Met) at this p osition, raising the possibility that this change may be tolerated. In summary, while the clinical significance of the Thr16829Met variant is uncertain, these d ata suggest that it is more likely to be benign. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Oct 23, 2017 | - - |
Cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Jun 02, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at