2-178776491-G-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6BP7
The NM_001267550.2(TTN):c.5373C>A(p.Thr1791Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000466 in 1,607,952 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 Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001267550.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.5373C>A | p.Thr1791Thr | synonymous_variant | Exon 28 of 363 | ENST00000589042.5 | NP_001254479.2 | |
TTN | NM_133379.5 | c.5373C>A | p.Thr1791Thr | synonymous_variant | Exon 28 of 46 | ENST00000360870.10 | NP_596870.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.5373C>A | p.Thr1791Thr | synonymous_variant | Exon 28 of 363 | 5 | NM_001267550.2 | ENSP00000467141.1 | ||
TTN | ENST00000360870.10 | c.5373C>A | p.Thr1791Thr | synonymous_variant | Exon 28 of 46 | 5 | NM_133379.5 | ENSP00000354117.4 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152142Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000364 AC: 9AN: 246992Hom.: 0 AF XY: 0.0000598 AC XY: 8AN XY: 133840
GnomAD4 exome AF: 0.0000495 AC: 72AN: 1455810Hom.: 0 Cov.: 33 AF XY: 0.0000469 AC XY: 34AN XY: 724530
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152142Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0AN XY: 74300
ClinVar
Submissions by phenotype
not specified Benign:2
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Thr1791Thr in exon 28 of TTN: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. Thr1791Thr in exon 28 of TTN: (allele freque ncy = n/a) -
not provided Uncertain:1
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Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
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Cardiovascular phenotype Benign:1
This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at