rs377296133
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001267550.2(TTN):āc.11063T>Cā(p.Phe3688Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000229 in 1,613,692 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
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.11063T>C | p.Phe3688Ser | missense_variant | 46/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.10303+2571T>C | intron_variant | ENST00000360870.10 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.11063T>C | p.Phe3688Ser | missense_variant | 46/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.10303+2571T>C | intron_variant | 5 | NM_133379.5 | ||||
TTN-AS1 | ENST00000659121.1 | n.1280+91A>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000460 AC: 7AN: 152180Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000402 AC: 10AN: 248602Hom.: 0 AF XY: 0.0000371 AC XY: 5AN XY: 134864
GnomAD4 exome AF: 0.0000205 AC: 30AN: 1461512Hom.: 0 Cov.: 33 AF XY: 0.0000206 AC XY: 15AN XY: 727046
GnomAD4 genome ? AF: 0.0000460 AC: 7AN: 152180Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74356
ClinVar
Submissions by phenotype
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2023 | TTN: PM2, BP4 - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 10, 2014 | Phe3517Ser in exon 44B of TTN: This variant is not expected to have clinical sig nificance due to a lack of conservation across species, including mammals. Of no te, >30 mammals have a serine (Ser) at this position despite high nearby amino a cid conservation. In addition, computational prediction tools do not suggest a h igh likelihood of impact to the protein. It has also been identified in 1/8226 European American chromosomes by the NHLBI Exome Sequencing Project (http://evs. gs.washington.edu/EVS/; dbSNP rs377296133). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at