rs397517780
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.99814C>T(p.Leu33272Phe) variant causes a missense change. The variant allele was found at a frequency of 0.0000158 in 1,453,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. L33272L) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.99814C>T | p.Leu33272Phe | missense_variant | 355/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.349G>A | non_coding_transcript_exon_variant | 4/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.99814C>T | p.Leu33272Phe | missense_variant | 355/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.416+13757G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 exomes AF: 0.00000409 AC: 1AN: 244732Hom.: 0 AF XY: 0.00000754 AC XY: 1AN XY: 132708
GnomAD4 exome AF: 0.0000158 AC: 23AN: 1453490Hom.: 0 Cov.: 33 AF XY: 0.0000180 AC XY: 13AN XY: 721544
GnomAD4 genome ? Cov.: 33
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 24, 2012 | The Leu30704Phe variant (TTN) has not been reported in the literature nor previo usly identified by our laboratory. Leucine (Leu) at position 30704 is highly con served in mammals and across evolutionarily distant species and the change to ph enylalanine (Phe) may not be tolerated. Other computational analyses (biochemica l amino acid properties, AlignGVGD, PolyPhen2, and SIFT) do not provide strong s upport for or against an impact to the protein. In summary, additional informati on is needed to fully assess the clinical significance of the Leu30704Phe varian t. - |
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 | Jul 29, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at