rs147879266
Variant summary
Our verdict is Likely benign. Variant got -3 ACMG points: 1P and 4B. PP2BP4_Strong
The NM_001267550.2(TTN):c.14339G>A(p.Ser4780Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000044 in 1,613,716 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/18 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -3 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.14339G>A | p.Ser4780Asn | missense_variant | 49/363 | ENST00000589042.5 | NP_001254479.2 | |
LOC124906101 | XR_007087319.1 | n.486C>T | non_coding_transcript_exon_variant | 2/2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.14339G>A | p.Ser4780Asn | missense_variant | 49/363 | 5 | NM_001267550.2 | ENSP00000467141 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.954C>T | non_coding_transcript_exon_variant | 5/13 |
Frequencies
GnomAD3 genomes AF: 0.0000526 AC: 8AN: 152170Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000966 AC: 24AN: 248460Hom.: 0 AF XY: 0.0000890 AC XY: 12AN XY: 134794
GnomAD4 exome AF: 0.0000431 AC: 63AN: 1461428Hom.: 1 Cov.: 30 AF XY: 0.0000440 AC XY: 32AN XY: 726986
GnomAD4 genome AF: 0.0000525 AC: 8AN: 152288Hom.: 0 Cov.: 32 AF XY: 0.0000537 AC XY: 4AN XY: 74460
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 15, 2020 | See Variant Classification Assertion Criteria. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Feb 06, 2021 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 14, 2018 | - - |
Dilated cardiomyopathy 1G Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Feb 22, 2002 | - - |
TTN-related disorder Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Aug 30, 2024 | The TTN c.14339G>A variant is predicted to result in the amino acid substitution p.Ser4780Asn. This variant has been reported in an individual with dilated cardiomyopathy (described as p.Ser4465Asn, Itoh-Satoh et al. 2002. PubMed ID: 11846417). This variant is reported in 0.10% of alleles in individuals of East Asian descent in gnomAD. Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
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 | Jan 03, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at