ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.5585G>A (p.Arg1862His) (rs146228576)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182534 SCV000234882 uncertain significance not provided 2018-05-02 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the MYH11 gene. The R1862H variant has not been published as pathogenic or been reported as benign to our knowledge. This variant is observed in 127/277052 (0.05%) alleles from individuals of multiple ethnic backgrounds, including 90/10148 (0.9%) Ashkenazi Jewish alleles, in large population cohorts (Lek et al., 2016). The R1862H variant has also been identified independently and/or in conjunction with additional cardiogenetic variants in multiple individuals referred for cardiogenetic testing at GeneDx. So far, segregation data is limited or absent for these individuals. The R1862H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. Nevertheless, in silico analyses, including protein predictors and evolutionary conservation, support a deleterious effect. Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or rare benign.
Illumina Clinical Services Laboratory,Illumina RCV000280640 SCV000395200 uncertain significance Lissencephaly, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV001085094 SCV000543722 benign Aortic aneurysm, familial thoracic 4 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000617240 SCV000739196 uncertain significance Cardiovascular phenotype 2016-11-30 criteria provided, single submitter clinical testing The p.R1862H variant (also known as c.5585G>A), located in coding exon 38 of the MYH11 gene, results from a G to A substitution at nucleotide position 5585. The arginine at codon 1862 is replaced by histidine, an amino acid with highly similar properties. Based on data from gnomAD, the A allele has an overall frequency of approximately 0.04% (127/282506) total alleles studied. The highest observed frequency was 0.88% (89/10158) of Ashkenazi Jewish alleles. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color RCV000776147 SCV000911145 benign Familial thoracic aortic aneurysm and aortic dissection 2018-04-07 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001085094 SCV001279560 uncertain significance Aortic aneurysm, familial thoracic 4 2017-04-27 criteria provided, single submitter clinical testing 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000776147 SCV001333415 benign Familial thoracic aortic aneurysm and aortic dissection 2018-03-23 criteria provided, single submitter clinical testing

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