rs397517537
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_001267550.2(TTN):c.31255C>T(p.Pro10419Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,104 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 Uncertain significance (★★).
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.31255C>T | p.Pro10419Ser | missense_variant | 115/363 | ENST00000589042.5 | NP_001254479.2 | |
LOC124907912 | XR_007087321.1 | n.7226G>A | non_coding_transcript_exon_variant | 1/2 | ||||
LOC124906100 | XR_007087318.1 | n.2186-18391G>A | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.31255C>T | p.Pro10419Ser | missense_variant | 115/363 | 5 | NM_001267550.2 | ENSP00000467141 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-39141G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD4 exome AF: 6.85e-7 AC: 1AN: 1460104Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1AN XY: 726372
GnomAD4 genome Cov.: 32
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 | Feb 25, 2015 | The p.Pro9175Ser variant in TTN has been identified by our laboratory in 1 Cauca sian individual with HCM who carried a pathogenic variant in another gene. In ad dition, this variant was absent from large population studies. Proline (Pro) at position 9175 is not conserved in mammals or evolutionarily distant species, sug gesting that a change at this position may be tolerated. Additional computationa l prediction tools do not provide strong support for or against an impact to the protein. In summary, the clinical significance of the p.Pro9175Ser variant is u ncertain. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1838244:Tibial muscular dystrophy;C1858763:Dilated cardiomyopathy 1G;C1861065:Hypertrophic cardiomyopathy 9;C1863599:Myopathy, myofibrillar, 9, with early respiratory failure;C2673677:Early-onset myopathy with fatal cardiomyopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Aug 17, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at