rs72648909
Variant summary
Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2
The NM_133379.5(TTN):c.14806A>T(p.Thr4936Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000712 in 1,613,260 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/15 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_133379.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -8 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_133379.5 | c.14806A>T | p.Thr4936Ser | missense_variant | 46/46 | ENST00000360870.10 | |
TTN | NM_001267550.2 | c.11311+5530A>T | intron_variant | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000360870.10 | c.14806A>T | p.Thr4936Ser | missense_variant | 46/46 | 5 | NM_133379.5 | ||
TTN | ENST00000589042.5 | c.11311+5530A>T | intron_variant | 5 | NM_001267550.2 | P1 | |||
TTN-AS1 | ENST00000659121.1 | n.1223+4624T>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.000434 AC: 66AN: 151920Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000523 AC: 131AN: 250424Hom.: 0 AF XY: 0.000584 AC XY: 79AN XY: 135320
GnomAD4 exome AF: 0.000741 AC: 1083AN: 1461222Hom.: 2 Cov.: 34 AF XY: 0.000737 AC XY: 536AN XY: 726926
GnomAD4 genome ? AF: 0.000434 AC: 66AN: 152038Hom.: 1 Cov.: 32 AF XY: 0.000417 AC XY: 31AN XY: 74326
ClinVar
Submissions by phenotype
not provided Uncertain:3Benign:3Other:1
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Likely benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Likely benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 14, 2018 | - - |
not provided, no classification provided | clinical testing | GeneDx | Jul 28, 2014 | - - |
Likely benign, no assertion criteria provided | clinical testing | Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ | - | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2017 | - - |
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 18, 2021 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 28, 2021 | The p.Thr4936Ser variant in TTN is classified as likely benign because it has been identified in 0.09% (32/35326) of Latino chromosomes by gnomAD (http://gnomad.broadinstitute.org). It is also located in an exon that is not highly expressed in the heart and is only present in a transcript (Novex -3) whose function is unclear. ACMG/AMP Criteria applied: BP1, BS1. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at