rs376403373
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_001267550.2(TTN):c.95083G>A(p.Gly31695Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000856 in 1,613,078 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. G31695G) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.95083G>A | p.Gly31695Arg | missense_variant | 342/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2043+3887C>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.95083G>A | p.Gly31695Arg | missense_variant | 342/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.416+22612C>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.000105 AC: 16AN: 152160Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000524 AC: 13AN: 248302Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134682
GnomAD4 exome AF: 0.0000835 AC: 122AN: 1460918Hom.: 0 Cov.: 33 AF XY: 0.0000661 AC XY: 48AN XY: 726662
GnomAD4 genome AF: 0.000105 AC: 16AN: 152160Hom.: 0 Cov.: 33 AF XY: 0.0000404 AC XY: 3AN XY: 74334
ClinVar
Submissions by phenotype
not specified Uncertain:3
Uncertain significance, criteria provided, single submitter | clinical testing | Athena Diagnostics | Oct 28, 2016 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Apr 30, 2012 | The Gly29127Arg variant (TTN) has not previously been reported in the literature nor previously identified by our laboratory. This variant has been identified i n 0.06% (2/3250) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS/); however, thi s frequency is too low to confidently rule out a disease causing role. Computati onal analyses (biochemical amino acid properties, conservation, and SIFT) sugges t that this variant may impact the protein, though this information is not predi ctive enough to determine pathogenicity. In summary, additional information is n eeded to fully assess the clinical significance of the Gly29127Arg variant. - |
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Dec 31, 2014 | Missense variants in the TTN gene are considered 'unclassified' if they are not previously reported in the literature and do not have >1% frequency in the population to be considered a polymorphism. Research indicates that truncating mutations in the TTN gene are expected to account for approximately 25% of familial and 18% of sporadic idiopathic DCM; however, truncating variants in the TTN gene have been reported in approximately 3% of reported control alleles. There has been little investigation into non-truncating variants. (Herman D et al. Truncations of titin causing dilated cardiomyopathy. N Eng J Med 366:619-628, 2012) The variant is found in DCM panel(s). - |
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | Jul 18, 2019 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jun 09, 2016 | - - |
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 31, 2018 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at