rs397517669
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4_Moderate
The NM_001267550.2(TTN):āc.67487A>Gā(p.Lys22496Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000144 in 1,461,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ). Synonymous variant affecting the same amino acid position (i.e. K22496K) has been classified as Likely benign.
Frequency
Consequence
NM_001267550.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -1 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.67487A>G | p.Lys22496Arg | missense_variant | 319/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2044-2862T>C | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.67487A>G | p.Lys22496Arg | missense_variant | 319/363 | 5 | NM_001267550.2 | P1 | |
ENST00000603521.1 | n.921T>C | non_coding_transcript_exon_variant | 1/1 | ||||||
TTN-AS1 | ENST00000659121.1 | n.417-17886T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248088Hom.: 0 AF XY: 0.00000743 AC XY: 1AN XY: 134552
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461156Hom.: 0 Cov.: 34 AF XY: 0.0000138 AC XY: 10AN XY: 726866
GnomAD4 genome ? Cov.: 32
ClinVar
Submissions by phenotype
not specified Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Feb 13, 2012 | The Lys19928Arg variant (TTN) has not been reported in the literature nor previo usly identified by our laboratory. Lysine (Lys) at position 19928 is highly cons erved in mammals and across evolutionarily distant species, though computational analyses (biochemical amino acid properties, AlignGVGD, and SIFT) do not provid e strong support for or against an impact to the protein. Additional information is needed to fully assess the clinical significance of the Lys19928Arg variant. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Aug 03, 2022 | Variant summary: TTN c.59783A>G (p.Lys19928Arg) results in a conservative amino acid change located in the A-band region, Fibronectin type-III domain of the encoded protein sequence. Three of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 248088 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.59783A>G in individuals affected with Limb-Girdle Muscular Dystrophy, Type 2J and no experimental evidence demonstrating its impact on protein function have been reported. One ClinVar submitter has assessed the variant since 2014: the variant was classified as of uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Autosomal recessive limb-girdle muscular dystrophy type 2J Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Apr 12, 2020 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
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 | Nov 09, 2021 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at