rs727504975
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 1P and 16B. PP2BP4_StrongBP6_Very_StrongBS2
The NM_001267550.2(TTN):c.21980C>T(p.Thr7327Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000875 in 1,610,976 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -15 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.21980C>T | p.Thr7327Met | missense_variant | 76/363 | ENST00000589042.5 | NP_001254479.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.21980C>T | p.Thr7327Met | missense_variant | 76/363 | 5 | NM_001267550.2 | ENSP00000467141 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-11585G>A | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000658 AC: 10AN: 152060Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000155 AC: 38AN: 244916Hom.: 1 AF XY: 0.000211 AC XY: 28AN XY: 132884
GnomAD4 exome AF: 0.0000898 AC: 131AN: 1458916Hom.: 2 Cov.: 34 AF XY: 0.000135 AC XY: 98AN XY: 725464
GnomAD4 genome AF: 0.0000658 AC: 10AN: 152060Hom.: 0 Cov.: 33 AF XY: 0.0000673 AC XY: 5AN XY: 74268
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 21, 2014 | Thr6083Met in exon 73 of TTN: This variant is not expected to have clinical sign ificance due to a lack of conservation across species, including mammals. Of not e, 6 mammals (squirrel monkey, bushbaby, alpaca, walrus, flying fox, and armadil lo) have a methionine (Met) at this position despite high nearby amino acid cons ervation. Thr6083Met in exon 73 of TTN (allele frequency = n/a) - |
Autosomal recessive limb-girdle muscular dystrophy type 2J;C1858763:Dilated cardiomyopathy 1G Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Nov 17, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Feb 01, 2024 | TTN: BP4 - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at