rs575070622
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 1P and 3B. PP2BP4_ModerateBP6
The NM_001267550.2(TTN):āc.106511G>Cā(p.Ser35504Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000344 in 1,599,012 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S35504I) has been classified 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 -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.106511G>C | p.Ser35504Thr | missense_variant | 359/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.220-5752C>G | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.106511G>C | p.Ser35504Thr | missense_variant | 359/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.416+6344C>G | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000723 AC: 11AN: 152154Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000340 AC: 8AN: 235286Hom.: 0 AF XY: 0.0000392 AC XY: 5AN XY: 127516
GnomAD4 exome AF: 0.0000304 AC: 44AN: 1446740Hom.: 0 Cov.: 32 AF XY: 0.0000278 AC XY: 20AN XY: 718946
GnomAD4 genome ? AF: 0.0000722 AC: 11AN: 152272Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74458
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | TTN: BP4 - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Dec 29, 2020 | - - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Nov 06, 2017 | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Nov 01, 2019 | The p.S26439T variant (also known as c.79316G>C), located in coding exon 186 of the TTN gene, results from a G to C substitution at nucleotide position 79316. The serine at codon 26439 is replaced by threonine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. 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