2-178800417-C-T
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7
The NM_001267550.2(TTN):c.561G>A(p.Ser187Ser) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000855 in 1,613,960 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 Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. S187S) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.561G>A | p.Ser187Ser | synonymous_variant | Exon 4 of 363 | ENST00000589042.5 | NP_001254479.2 | |
TTN | NM_133379.5 | c.561G>A | p.Ser187Ser | synonymous_variant | Exon 4 of 46 | ENST00000360870.10 | NP_596870.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.561G>A | p.Ser187Ser | synonymous_variant | Exon 4 of 363 | 5 | NM_001267550.2 | ENSP00000467141.1 | ||
TTN | ENST00000360870.10 | c.561G>A | p.Ser187Ser | synonymous_variant | Exon 4 of 46 | 5 | NM_133379.5 | ENSP00000354117.4 |
Frequencies
GnomAD3 genomes AF: 0.0000657 AC: 10AN: 152130Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000195 AC: 49AN: 251278Hom.: 0 AF XY: 0.000162 AC XY: 22AN XY: 135796
GnomAD4 exome AF: 0.0000876 AC: 128AN: 1461830Hom.: 0 Cov.: 31 AF XY: 0.0000908 AC XY: 66AN XY: 727224
GnomAD4 genome AF: 0.0000657 AC: 10AN: 152130Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5AN XY: 74312
ClinVar
Submissions by phenotype
not specified Benign:2
p.Ser187Ser in Exon 04 of TTN: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence. It has been identified in 2/7020 European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS; dbSNP rs141444282). -
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not provided Benign:2
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TTN: BP4, BP7 -
Autosomal recessive limb-girdle muscular dystrophy type 2J Benign:1
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Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
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Cardiomyopathy Benign:1
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Early-onset myopathy with fatal cardiomyopathy Benign:1
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Tibial muscular dystrophy Benign:1
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Myopathy, myofibrillar, 9, with early respiratory failure 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