rs727503539
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.97480C>T(p.Arg32494Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000124 in 1,607,130 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 (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R32494H) 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.97480C>T | p.Arg32494Cys | missense_variant | 349/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.1958G>A | non_coding_transcript_exon_variant | 7/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.97480C>T | p.Arg32494Cys | missense_variant | 349/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.416+18640G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152104Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000207 AC: 5AN: 241684Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 131130
GnomAD4 exome AF: 0.00000893 AC: 13AN: 1455026Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1AN XY: 722840
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152104Hom.: 0 Cov.: 32 AF XY: 0.0000538 AC XY: 4AN XY: 74286
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 | Jul 25, 2014 | The Arg29926Cys variant in TTN has not been previously reported in individuals w ith cardiomyopathy and was absent from large population studies. Computational p rediction tools and conservation analyses do not provide strong support for or a gainst an impact to the protein. In summary, the clinical significance of the Ar g29926Cys variant is uncertain. - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 23, 2018 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 02, 2013 | There is insufficient or conflicting evidence for classification of this alteration. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at