rs571231816
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001267550.2(TTN):c.19996C>T(p.Pro6666Ser) variant causes a missense, splice region change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000215 in 1,582,148 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. 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. P6666A) has been classified as Uncertain significance.
Frequency
Consequence
NM_001267550.2 missense, splice_region
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.19996C>T | p.Pro6666Ser | missense_variant, splice_region_variant | 69/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.19996C>T | p.Pro6666Ser | missense_variant, splice_region_variant | 69/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-7135G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152094Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.00000450 AC: 1AN: 222124Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 120124
GnomAD4 exome AF: 0.0000189 AC: 27AN: 1430054Hom.: 0 Cov.: 30 AF XY: 0.0000198 AC XY: 14AN XY: 708650
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152094Hom.: 0 Cov.: 33 AF XY: 0.0000539 AC XY: 4AN XY: 74280
ClinVar
Submissions by phenotype
not provided Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Dec 03, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 09, 2023 | Has not been previously published as pathogenic or benign to our knowledge; Missense variant in a gene in which most reported pathogenic variants are truncating/loss-of-function; Not observed at significant frequency in large population cohorts (gnomAD) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Nov 14, 2014 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 27, 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 | Oct 14, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at