18-3067274-C-CT
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Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 4P and 8B. PM2PM4BP6_Very_Strong
The NM_003803.4(MYOM1):βc.5045_5046insAβ(p.Lys1683GlufsTer16) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000098 in 1,601,790 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (β β ).
Frequency
Genomes: π 0.00058 ( 0 hom., cov: 33)
Exomes π: 0.000048 ( 0 hom. )
Consequence
MYOM1
NM_003803.4 frameshift
NM_003803.4 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 0.900
Genes affected
MYOM1 (HGNC:7613): (myomesin 1) The giant protein titin, together with its associated proteins, interconnects the major structure of sarcomeres, the M bands and Z discs. The C-terminal end of the titin string extends into the M line, where it binds tightly to M-band constituents of apparent molecular masses of 190 kD (myomesin 1) and 165 kD (myomesin 2). This protein, myomesin 1, like myomesin 2, titin, and other myofibrillar proteins contains structural modules with strong homology to either fibronectin type III (motif I) or immunoglobulin C2 (motif II) domains. Myomesin 1 and myomesin 2 each have a unique N-terminal region followed by 12 modules of motif I or motif II, in the arrangement II-II-I-I-I-I-I-II-II-II-II-II. The two proteins share 50% sequence identity in this repeat-containing region. The head structure formed by these 2 proteins on one end of the titin string extends into the center of the M band. The integrating structure of the sarcomere arises from muscle-specific members of the superfamily of immunoglobulin-like proteins. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
PM4
Frameshift in the end of transcript resulting in stoplost. Downstream stopcodon found after 1690 codons.
BP6
Variant 18-3067274-C-CT is Benign according to our data. Variant chr18-3067274-C-CT is described in ClinVar as [Likely_benign]. Clinvar id is 227706.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
MYOM1 | NM_003803.4 | c.5045_5046insA | p.Lys1683GlufsTer16 | frameshift_variant | 38/38 | ENST00000356443.9 | NP_003794.3 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
MYOM1 | ENST00000356443.9 | c.5045_5046insA | p.Lys1683GlufsTer16 | frameshift_variant | 38/38 | 1 | NM_003803.4 | ENSP00000348821 | P2 | |
MYOM1 | ENST00000261606.11 | c.4757_4758insA | p.Lys1587GlufsTer16 | frameshift_variant | 37/37 | 1 | ENSP00000261606 | A2 | ||
MYOM1 | ENST00000581804.1 | n.535_536insA | non_coding_transcript_exon_variant | 3/3 | 3 |
Frequencies
GnomAD3 genomes AF: 0.000585 AC: 89AN: 152236Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000125 AC: 29AN: 232268Hom.: 0 AF XY: 0.0000874 AC XY: 11AN XY: 125910
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GnomAD4 exome AF: 0.0000476 AC: 69AN: 1449436Hom.: 0 Cov.: 29 AF XY: 0.0000472 AC XY: 34AN XY: 719896
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GnomAD4 genome AF: 0.000578 AC: 88AN: 152354Hom.: 0 Cov.: 33 AF XY: 0.000617 AC XY: 46AN XY: 74514
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Dec 23, 2015 | p.Lys1683fs in exon 38 of MYOM1: This variant is predicted to cause a frameshift within the last exon and is predicted to result in a protein where the last few amino acids are replaced by different residues. This variant is not expected to have clinical significance because it has been identified in 0.3% (15/4502) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broad institute.org; dbSNP rs573184538). - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 21, 2023 | - - |
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at