ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.5566C>T (p.Leu1856=)

gnomAD frequency: 0.00150  dbSNP: rs142639688
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Total submissions: 15
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000126967 SCV000170498 benign not specified 2013-10-14 criteria provided, single submitter clinical testing 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.
Ambry Genetics RCV000242448 SCV000319215 likely benign Familial thoracic aortic aneurysm and aortic dissection 2015-03-04 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina RCV000242448 SCV000395201 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2016-06-14 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV000371604 SCV000395202 uncertain significance Lissencephaly, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000464298 SCV000556091 benign Aortic aneurysm, familial thoracic 4 2024-01-31 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001092817 SCV000604338 benign not provided 2023-10-16 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000464298 SCV000745472 likely benign Aortic aneurysm, familial thoracic 4 2017-06-28 criteria provided, single submitter clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc RCV000680549 SCV000807960 likely benign Connective tissue disorder 2018-06-01 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000242448 SCV000902158 benign Familial thoracic aortic aneurysm and aortic dissection 2016-08-16 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000242448 SCV000911314 benign Familial thoracic aortic aneurysm and aortic dissection 2018-03-07 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000126967 SCV000917828 benign not specified 2018-05-14 criteria provided, single submitter clinical testing Variant summary: MYH11 c.5587C>T alters a non-conserved nucleotide resulting in a synonymous change. 5/5 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 0.0013 in 277156 control chromosomes in the gnomAD database, including 1 homozygotes. The observed variant frequency is approximately 1048-fold higher than the estimated maximal expected allele frequency for a pathogenic variant in MYH11 causing Aortopathy phenotype (1.3e-06), strongly suggesting that the variant is benign. The variant, c.5587C>T, has been reported in the literature in one individual affected with Aortopathy (van de Luijtgaarden_2015). This report does not provide unequivocal conclusions about association of the variant with Aortopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign/benign." Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen RCV001092817 SCV001249510 likely benign not provided 2024-08-01 criteria provided, single submitter clinical testing MYH11: BP4, BP7
Illumina Laboratory Services, Illumina RCV000464298 SCV001279561 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.
Genome Diagnostics Laboratory, Amsterdam University Medical Center RCV000464298 SCV000745953 likely benign Aortic aneurysm, familial thoracic 4 2014-11-19 no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV001092817 SCV001926941 likely benign not provided no assertion criteria provided clinical testing

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