rs766921440
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_001267550.2(TTN):c.39115A>C(p.Thr13039Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000558 in 1,612,540 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/17 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 -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.39115A>C | p.Thr13039Pro | missense_variant | 202/363 | ENST00000589042.5 | |
LOC124906100 | XR_007087318.1 | n.2185+7969T>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.39115A>C | p.Thr13039Pro | missense_variant | 202/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.502+54789T>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000199 AC: 3AN: 151124Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000806 AC: 2AN: 248014Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134662
GnomAD4 exome AF: 0.00000411 AC: 6AN: 1461300Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 726932
GnomAD4 genome ? AF: 0.0000198 AC: 3AN: 151240Hom.: 0 Cov.: 32 AF XY: 0.0000271 AC XY: 2AN XY: 73920
ClinVar
Submissions by phenotype
Tip-toe gait Pathogenic:1
Likely pathogenic, no assertion criteria provided | clinical testing | Practice for Gait Abnormalities, David Pomarino, Competency Network Toe Walking c/o Practice Pomarino | - | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Nov 03, 2015 | Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in DCM-CRDM panel(s). - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Dec 21, 2017 | - - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Aug 17, 2018 | - - |
TTN-related condition Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 02, 2023 | The TTN c.39115A>C variant is predicted to result in the amino acid substitution p.Thr13039Pro. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.013% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-179517197-T-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at