rs146241078
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.4321C>T(p.Arg1441Cys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000372 in 1,613,842 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R1441H) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.4321C>T | p.Arg1441Cys | missense_variant | 25/363 | ENST00000589042.5 | |
TTN | NM_133379.5 | c.4321C>T | p.Arg1441Cys | missense_variant | 25/46 | ENST00000360870.10 | |
LOC101927055 | NR_120594.1 | n.938G>A | non_coding_transcript_exon_variant | 1/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.4321C>T | p.Arg1441Cys | missense_variant | 25/363 | 5 | NM_001267550.2 | P1 | |
TTN | ENST00000360870.10 | c.4321C>T | p.Arg1441Cys | missense_variant | 25/46 | 5 | NM_133379.5 | ||
TTN-AS1 | ENST00000659121.1 | n.5290G>A | non_coding_transcript_exon_variant | 12/13 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152110Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000239 AC: 6AN: 250864Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135568
GnomAD4 exome AF: 0.0000369 AC: 54AN: 1461732Hom.: 0 Cov.: 34 AF XY: 0.0000358 AC XY: 26AN XY: 727166
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152110Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74316
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jun 04, 2021 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 28, 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 13, 2021 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 28, 2018 | The p.R1395C variant (also known as c.4183C>T), located in coding exon 23 of the TTN gene, results from a C to T substitution at nucleotide position 4183. The arginine at codon 1395 is replaced by cysteine, an amino acid with highly dissimilar properties. This alteration has been reported as a secondary cardiac variant in an exome cohort (reported as p.R1441C (c.4321C>T)) (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46). This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at