rs727504736
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001267550.2(TTN):c.21544C>T(p.Arg7182Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000428 in 1,613,186 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R7182Q) has been classified as Likely benign.
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/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.21544C>T | p.Arg7182Trp | missense_variant | 74/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.21544C>T | p.Arg7182Trp | missense_variant | 74/363 | 5 | NM_001267550.2 | P1 | |
ENST00000590024.1 | n.100G>A | non_coding_transcript_exon_variant | 1/1 | ||||||
TTN-AS1 | ENST00000659121.1 | n.503-10948G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000329 AC: 5AN: 152036Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000926 AC: 23AN: 248366Hom.: 0 AF XY: 0.0000816 AC XY: 11AN XY: 134768
GnomAD4 exome AF: 0.0000438 AC: 64AN: 1461150Hom.: 0 Cov.: 33 AF XY: 0.0000399 AC XY: 29AN XY: 726862
GnomAD4 genome ? AF: 0.0000329 AC: 5AN: 152036Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74262
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 02, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 29, 2021 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jan 29, 2015 | Variant classified as Uncertain Significance - Favor Benign. The p.Arg5938Trp va riant in TTN has not been previously reported in any other families with cardiom yopathy. This variant has been identified in 8/11348 Latino chromosomes by the E xome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Arginine (Ar g) at position 5938 is not conserved in mammals or in evolutionarily distant spe cies and one primate (gorilla) has a tryptophan (Trp) at this position, raising the possibility that this change is tolerated. In summary, while the clinical si gnificance of the p.Arg5938Trp variant is uncertain, the presence of the variant amino acid in another primate as well as its the presence in the general popula tion suggests that it is more likely to be benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at