rs199577321
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 3P and 1B. PP2PP3_ModerateBP6
The NM_000257.4(MYH7):c.28G>C(p.Gly10Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000217 in 1,614,094 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G10A) has been classified as Uncertain significance.
Frequency
Consequence
NM_000257.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
MYH7 | NM_000257.4 | c.28G>C | p.Gly10Arg | missense_variant | 3/40 | ENST00000355349.4 | |
MYH7 | NM_001407004.1 | c.28G>C | p.Gly10Arg | missense_variant | 2/39 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
MYH7 | ENST00000355349.4 | c.28G>C | p.Gly10Arg | missense_variant | 3/40 | 1 | NM_000257.4 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152278Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000677 AC: 17AN: 251226Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135772
GnomAD4 exome AF: 0.0000198 AC: 29AN: 1461816Hom.: 0 Cov.: 35 AF XY: 0.0000206 AC XY: 15AN XY: 727208
GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152278Hom.: 0 Cov.: 33 AF XY: 0.0000403 AC XY: 3AN XY: 74406
ClinVar
Submissions by phenotype
Cardiomyopathy Benign:3
Likely benign, criteria provided, single submitter | clinical testing | All of Us Research Program, National Institutes of Health | Jan 11, 2024 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Color Diagnostics, LLC DBA Color Health | Sep 23, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario | Nov 10, 2017 | - - |
Dilated cardiomyopathy 1S Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Myosin storage myopathy Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Mar 12, 2024 | The p.G10R variant (also known as c.28G>C), located in coding exon 1 of the MYH7 gene, results from a G to C substitution at nucleotide position 28. The glycine at codon 10 is replaced by arginine, an amino acid with dissimilar properties. This variant has been reported in association with hypertrophic cardiomyopathy (HCM) and pediatric cardiomyopathy; however it has also been seen in exome and healthy cohorts (Ng D et al. Circ Cardiovasc Genet, 2013 Aug;6:337-46; Walsh R et al. Genet Med, 2017 Feb;19:192-203; Harper AR et al. Nat Genet, 2021 Feb;53:135-142; Ware SM et al. Am J Hum Genet, 2022 Feb;109:282-298; Park J et al. Hum Mol Genet, 2022 Mar;31:827-837). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear. - |
Hypertrophic cardiomyopathy 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Mar 09, 2018 | p.Gly10Arg in exon 3 of MYH7: This variant is not expected to have clinical sign ificance because it has been identified in 0.15% of Ashkenazi Jewish chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; d bSNP rs199577321). ACMG/AMP Criteria Applied: BS1. - |
MYH7-related skeletal myopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | research | Biesecker Lab/Clinical Genomics Section, National Institutes of Health | Jun 24, 2013 | - - |
Hypertrophic cardiomyopathy Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 19, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at