rs370878527
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP6
The NM_001267550.2(TTN):c.65371G>A(p.Gly21791Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000621 in 1,609,806 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Synonymous variant affecting the same amino acid position (i.e. G21791G) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
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.65371G>A | p.Gly21791Ser | missense_variant | 312/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2657C>T | non_coding_transcript_exon_variant | 10/17 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.65371G>A | p.Gly21791Ser | missense_variant | 312/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-13785C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000395 AC: 6AN: 152006Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000165 AC: 4AN: 242110Hom.: 0 AF XY: 0.0000153 AC XY: 2AN XY: 131078
GnomAD4 exome AF: 0.0000645 AC: 94AN: 1457800Hom.: 0 Cov.: 31 AF XY: 0.0000635 AC XY: 46AN XY: 724828
GnomAD4 genome ? AF: 0.0000395 AC: 6AN: 152006Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74220
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Sep 26, 2014 | The Gly19223Ser variant in TTN has previously been identified by our laboratory in 1 adolescent with HCM. This variant has also been identified in 1/8234 Europe an American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.was hington.edu/EVS/; dbSNP rs370878527). Computational prediction tools and conserv ation analysis do not provide strong support for or against an impact to the pro tein. In summary, the clinical significance of the Gly19223Ser variant is uncert ain. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 24, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at