2-178732218-A-T
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 1P and 2B. PP2BP4BP6
The NM_001267550.2(TTN):c.16751T>A(p.Ile5584Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000514 in 1,613,680 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I5584L) has been classified as Uncertain significance.
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.16751T>A | p.Ile5584Asn | missense_variant | 57/363 | ENST00000589042.5 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.16751T>A | p.Ile5584Asn | missense_variant | 57/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.503-2286A>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152108Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.000121 AC: 30AN: 248610Hom.: 0 AF XY: 0.000185 AC XY: 25AN XY: 134832
GnomAD4 exome AF: 0.0000561 AC: 82AN: 1461572Hom.: 1 Cov.: 36 AF XY: 0.0000990 AC XY: 72AN XY: 727064
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152108Hom.: 0 Cov.: 33 AF XY: 0.0000135 AC XY: 1AN XY: 74292
ClinVar
Submissions by phenotype
not specified Uncertain:1Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jan 24, 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 | May 07, 2015 | Variant classified as Uncertain Significance - Favor Benign. The p.Ile4340Asn va riant in TTN has not been previously reported in individuals with cardiomyopathy , but has been identified in 0.1% (17/16512) of South Asian chromosomes by the E xome Aggregation Consortium (ExAC, http://exac.broadinstitute.org). Computationa l prediction tools and conservation analysis do not provide strong support for o r against an impact to the protein. In summary, while the clinical significance of the p.Ile4340Asn variant is uncertain, its frequency suggests that it is more likely to be benign. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at