rs727503705
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):c.1429A>T(p.Thr477Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000143 in 1,613,970 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/18 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.1429A>T | p.Thr477Ser | missense_variant | 9/363 | ENST00000589042.5 | NP_001254479.2 | |
TTN | NM_133379.5 | c.1429A>T | p.Thr477Ser | missense_variant | 9/46 | ENST00000360870.10 | NP_596870.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.1429A>T | p.Thr477Ser | missense_variant | 9/363 | 5 | NM_001267550.2 | ENSP00000467141 | P1 | |
TTN | ENST00000360870.10 | c.1429A>T | p.Thr477Ser | missense_variant | 9/46 | 5 | NM_133379.5 | ENSP00000354117 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251334Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135856
GnomAD4 exome AF: 0.0000151 AC: 22AN: 1461750Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727172
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152220Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74366
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 | Apr 20, 2013 | Variant classified as Uncertain Significance - Favor Benign. The Thr477Ser varia nt in TTN has not been reported in individuals with cardiomyopathy or in large p opulation studies. Threonine (Thr) at position 477 is not fully conserved in evo lutionarily distant species, and 2 mammals (rabbit and pika) carry a serine (Ser ; this variant) at this position, suggesting that this change may be tolerated. Other computational analyses (biochemical amino acid properties, AlignGVGD, Poly Phen2, and SIFT) do not provide strong support for or against an impact to the p rotein. Additional studies are needed to fully assess the clinical significance of this variant. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 28, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at