rs727503678
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_001267550.2(TTN):c.10046C>T(p.Thr3349Ile) variant causes a missense change. The variant allele was found at a frequency of 0.0000359 in 1,614,006 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T3349A) has been classified as Uncertain significance.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.10046C>T | p.Thr3349Ile | missense_variant | 43/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.10046C>T | p.Thr3349Ile | missense_variant | 43/46 | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.10046C>T | p.Thr3349Ile | missense_variant | 43/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.10046C>T | p.Thr3349Ile | missense_variant | 43/46 | 5 | NM_133379.5 | ||
TTN-AS1 | ENST00000659121.1 | n.1469G>A | non_coding_transcript_exon_variant | 10/13 |
Frequencies
GnomAD3 genomes AF: 0.0000723 AC: 11AN: 152204Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000167 AC: 42AN: 251236Hom.: 0 AF XY: 0.000155 AC XY: 21AN XY: 135766
GnomAD4 exome AF: 0.0000322 AC: 47AN: 1461802Hom.: 0 Cov.: 32 AF XY: 0.0000330 AC XY: 24AN XY: 727204
GnomAD4 genome AF: 0.0000723 AC: 11AN: 152204Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74354
ClinVar
Submissions by phenotype
not provided Uncertain:1Other:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Aug 17, 2020 | - - |
not provided, no classification provided | clinical testing | GeneDx | May 28, 2014 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 16, 2014 | The Thr3349Ile variant in TTN has not been reported in individuals with cardiomy opathy or in large population studies. Computational prediction tools and conser vation analysis do not provide strong support for or against an impact to the pr otein. Additional information is needed to fully assess the clinical significan ce of the variant. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 27, 2017 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1838244:Tibial muscular dystrophy;C1858763:Dilated cardiomyopathy 1G;C1861065:Hypertrophic cardiomyopathy 9;C1863599:Myopathy, myofibrillar, 9, with early respiratory failure;C2673677:Early-onset myopathy with fatal cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Nov 10, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 11, 2019 | The p.T3303I variant (also known as c.9908C>T), located in coding exon 41 of the TTN gene, results from a C to T substitution at nucleotide position 9908. The threonine at codon 3303 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at