rs149586047
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_133379.5(TTN):c.14240A>T(p.Asp4747Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000496 in 1,613,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_133379.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_133379.5 | c.14240A>T | p.Asp4747Val | missense_variant | 46/46 | ENST00000360870.10 | |
TTN | NM_001267550.2 | c.11311+4964A>T | intron_variant | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000360870.10 | c.14240A>T | p.Asp4747Val | missense_variant | 46/46 | 5 | NM_133379.5 | ||
TTN | ENST00000589042.5 | c.11311+4964A>T | intron_variant | 5 | NM_001267550.2 | P1 | |||
TTN-AS1 | ENST00000659121.1 | n.1223+5190T>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000289 AC: 44AN: 152002Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000481 AC: 12AN: 249502Hom.: 0 AF XY: 0.0000222 AC XY: 3AN XY: 135172
GnomAD4 exome AF: 0.0000240 AC: 35AN: 1461048Hom.: 0 Cov.: 35 AF XY: 0.0000138 AC XY: 10AN XY: 726832
GnomAD4 genome ? AF: 0.000296 AC: 45AN: 152120Hom.: 0 Cov.: 32 AF XY: 0.000255 AC XY: 19AN XY: 74372
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 | Oct 14, 2013 | Variant classified as Uncertain Significance - Favor Benign. The Asp4747Val vari ant in TTN has not been previously reported in individuals with cardiomyopathy, but has been identified in 0.2% (8/4404) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/; dbSNP rs14958 6047). Computational analyses are limited or unavailable for this variant. While this frequency suggests that this variant is more likely benign, it is too low to confidently rule out a disease-causing role. Additional information is needed to fully assess its clinical significance. - |
TTN-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 08, 2023 | The TTN c.14240A>T variant is predicted to result in the amino acid substitution p.Asp4747Val. This variant is referred to as c.11311+4964A>T (intronic) with an alternate transcript NM_001267550.2. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.061% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-179612887-T-A). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
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 20, 2021 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 27, 2017 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at