rs141926114
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate
The NM_133379.5(TTN):c.10625G>A(p.Arg3542Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000527 in 1,612,828 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/15 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. R3542W) has been classified as Uncertain significance.
Frequency
Consequence
NM_133379.5 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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_133379.5 | c.10625G>A | p.Arg3542Gln | missense_variant | 46/46 | ENST00000360870.10 | |
TTN | NM_001267550.2 | c.11311+1349G>A | intron_variant | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000360870.10 | c.10625G>A | p.Arg3542Gln | missense_variant | 46/46 | 5 | NM_133379.5 | ||
TTN | ENST00000589042.5 | c.11311+1349G>A | intron_variant | 5 | NM_001267550.2 | P1 | |||
TTN-AS1 | ENST00000659121.1 | n.1224-4491C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000178 AC: 27AN: 151800Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000760 AC: 19AN: 250104Hom.: 0 AF XY: 0.0000666 AC XY: 9AN XY: 135178
GnomAD4 exome AF: 0.0000397 AC: 58AN: 1461028Hom.: 0 Cov.: 39 AF XY: 0.0000385 AC XY: 28AN XY: 726812
GnomAD4 genome ? AF: 0.000178 AC: 27AN: 151800Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74114
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 | Sep 12, 2013 | The Arg3542Gln variant in TTN has not been reported in individuals with cardiomy opathy or been previously identified by our laboratory. This variant has been id entified in 1/4406 African American chromosomes by the NHLBI Exome Sequencing Pr oject (http://evs.gs.washington.edu/EVS/; dbSNP rs141926114). Computational anal yses are limited for this variant. Additional information is needed to fully ass ess the clinical significance of the Arg3542Gln variant. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at