chr2-178573416-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 1P and 0B. PP2
The NM_001267550.2(TTN):c.72716T>A(p.Met24239Lys) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000961 in 1,519,826 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. M24239T) has been classified as Uncertain significance.
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.72716T>A | p.Met24239Lys | missense_variant | 326/363 | ENST00000589042.5 | |
TTN-AS1 | NR_038272.1 | n.2044-9156A>T | intron_variant, non_coding_transcript_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
TTN | ENST00000589042.5 | c.72716T>A | p.Met24239Lys | missense_variant | 326/363 | 5 | NM_001267550.2 | P1 | |
TTN-AS1 | ENST00000659121.1 | n.417-24180A>T | intron_variant, non_coding_transcript_variant |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152070Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000455 AC: 8AN: 175928Hom.: 0 AF XY: 0.0000753 AC XY: 7AN XY: 92904
GnomAD4 exome AF: 0.000102 AC: 139AN: 1367756Hom.: 0 Cov.: 38 AF XY: 0.0000865 AC XY: 58AN XY: 670434
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152070Hom.: 0 Cov.: 32 AF XY: 0.0000539 AC XY: 4AN XY: 74268
ClinVar
Submissions by phenotype
not provided Uncertain:2Benign:1
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jul 11, 2018 | - - |
Uncertain significance, criteria provided, single submitter | clinical testing | Revvity Omics, Revvity | May 11, 2022 | - - |
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 20, 2018 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Nov 14, 2022 | Variant summary: TTN c.65012T>A (p.Met21671Lys) results in a non-conservative amino acid change located in the A-band region of the encoded protein sequence. Two of four in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.5e-05 in 175928 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.65012T>A has been reported in the literature in at least one individual affected with Cardiomyopathy without strong evidence of causality (Campuzano_2015, Martinez-Barrios_2022). These reports do not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as likely benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at