rs397517615
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_001267550.2(TTN):āc.54091A>Gā(p.Ser18031Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000806 in 1,612,744 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 Uncertain significance (ā ā ).
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.54091A>G | p.Ser18031Gly | missense_variant | Exon 280 of 363 | ENST00000589042.5 | NP_001254479.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.54091A>G | p.Ser18031Gly | missense_variant | Exon 280 of 363 | 5 | NM_001267550.2 | ENSP00000467141.1 |
Frequencies
GnomAD3 genomes AF: 0.0000395 AC: 6AN: 152000Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000807 AC: 2AN: 247778Hom.: 0 AF XY: 0.00000744 AC XY: 1AN XY: 134402
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1460744Hom.: 0 Cov.: 32 AF XY: 0.00000826 AC XY: 6AN XY: 726670
GnomAD4 genome AF: 0.0000395 AC: 6AN: 152000Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74224
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 14, 2019 | Not observed at a significant frequency in large population cohorts (Lek et al., 2016); Missense variant in a gene in which most reported pathogenic variants are truncating/loss-of-function; This variant is associated with the following publications: (PMID: 24503780) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 15, 2019 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 06, 2015 | The p.Ser15463Gly variant in TTN has been previously identified by our laborator y in 1 child with DCM who also carried a likely pathogenic variant in this gene. It has also been identified in 1/712 chromosomes of unspecified ancestry by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs397 517615). Computational prediction tools and conservation analysis do not provide strong support for or against an impact to the protein. In summary, the clinica l significance of the p.Ser15463Gly 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 | Nov 18, 2016 | - - |
Hypertrophic cardiomyopathy 9 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Clinical Genomics Laboratory, Washington University in St. Louis | Oct 17, 2024 | The TTN c.54091A>G (p.Ser18031Gly) variant, to our knowledge, has not been reported in the medical literature. The highest population minor allele frequency in the population database genome aggregation database (v.2.1.1) is 0.02% in the other populations. This variant was reported in the ClinVar database as a variant of uncertain significance by four submitters (ClinVar ID: 47080). Computational predictors indicate this variant has no impact on TTN function. Due to limited information and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at