rs727503655
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP4_StrongBP6
The NM_001267550.2(TTN):āc.13499A>Gā(p.Lys4500Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,613,820 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/18 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 -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
TTN | NM_001267550.2 | c.13499A>G | p.Lys4500Arg | missense_variant | 48/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.13499A>G | p.Lys4500Arg | missense_variant | 48/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.1133+1441T>C | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152186Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000241 AC: 6AN: 248470Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134742
GnomAD4 exome AF: 0.0000246 AC: 36AN: 1461634Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 727102
GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152186Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74342
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Mar 13, 2018 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
Uncertain significance, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jun 19, 2014 | Variant classified as Uncertain Significance - Favor Benign. The Lys4262Arg vari ant in TTN has not been previously reported in individuals with cardiomyopathy o r in large population studies. Computational prediction tools and conservation a nalysis are limited, but suggest that this variant may not impact the protein, t hough this information is not predictive enough to rule out pathogenicity. In ad dition, 4 mammals (ferret, star-nosed mole, tenrec, and opossum) carry an argini ne (Arg) at this position, suggesting that this change may be tolerated. In sum mary, while the clinical significance of the Lys4262Arg variant is uncertain, th e presence of the variant amino acid in other mammals suggests that it is more l ikely to be benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at