ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.5869G>C (p.Glu1957Gln) (rs768140376)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Praxis fuer Humangenetik Tuebingen RCV000996215 SCV001150811 uncertain significance not provided 2018-05-01 criteria provided, single submitter clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV001027837 SCV001190457 uncertain significance Aortic aneurysm, familial thoracic 4 2019-10-02 criteria provided, single submitter clinical testing MYH11 NM_002474.2 exon 41 p.Glu1957Gln (c.5869G>C): This variant has not been reported in the literature but is present in 0.009% (11/113768) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/16-15797898-C-G). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Illumina Clinical Services Laboratory,Illumina RCV001027837 SCV001275639 uncertain significance Aortic aneurysm, familial thoracic 4 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Integrated Genetics/Laboratory Corporation of America RCV001174783 SCV001338116 likely benign not specified 2020-01-27 criteria provided, single submitter clinical testing Variant summary: MYH11 c.*91G>C (in transcript NM_001040113.1) alters a conserved nucleotide and is located in the untranslated mRNA region downstream of the termination codon. Additionally, 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 4.8e-05 in 251490 control chromosomes. The observed variant frequency is approximately 38 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYH11 causing Aortopathy phenotype (1.3e-06), and 3.8 fold of the estimated maximal expected allele frequency for a pathogenic variant in MYH11 causing Thoracic Aortic Aneurysms and Dissections with Patent Ductus Arteriosus phenotype (1.3e-05) strongly suggesting that the variant is benign. However, in the absence of phenotypic information, the possibility of subclinical presentations for cardiac conditions in the gnomAD control cohort cannot be entirely excluded. Pathogenic variants located in the C-terminal coiled-coil region of the MYH11 gene have been reported in individuals with thoracic aortic aneurysm and/or aortic dissection (TAAD) and patent ductus arteriosus (PDA). Mutations in MYH11 were originally been reported in 2 families with TAAD, who also presented with patent ductus arteriosus (PMID 16444274). To our knowledge, no occurrence of c.*91G>C in individuals affected with Thoracic Aortic Aneurysms and Dissections with Patent Ductus Arteriosus or Aortopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely benign until additional evidence supporting a disease association is identified.
Color RCV001181543 SCV001346717 likely benign Familial thoracic aortic aneurysm and aortic dissection 2018-06-25 criteria provided, single submitter clinical testing

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