ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.4835G>A (p.Arg1612His)

gnomAD frequency: 0.00003  dbSNP: rs781252922
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV000788703 SCV000927907 uncertain significance not provided 2018-09-03 criteria provided, single submitter clinical testing
Invitae RCV000795576 SCV000935044 uncertain significance Aortic aneurysm, familial thoracic 4 2022-06-04 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1619 of the MYH11 protein (p.Arg1619His). This variant is present in population databases (rs781252922, gnomAD 0.03%). This variant has not been reported in the literature in individuals affected with MYH11-related conditions. ClinVar contains an entry for this variant (Variation ID: 636781). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Color Diagnostics, LLC DBA Color Health RCV001525948 SCV001736168 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-06-21 criteria provided, single submitter clinical testing This missense variant replaces arginine with histidine at codon 1619 of the MYH11 protein. Computational prediction suggests that this variant may have deleterious impact on protein structure and function (internally defined REVEL score threshold >= 0.7, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with MYH11-related disorders in the literature. This variant has been identified in 7/251400 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Ambry Genetics RCV001525948 SCV002639211 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-01-07 criteria provided, single submitter clinical testing The p.R1612H variant (also known as c.4835G>A), located in coding exon 33 of the MYH11 gene, results from a G to A substitution at nucleotide position 4835. The arginine at codon 1612 is replaced by histidine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
Fulgent Genetics, Fulgent Genetics RCV002493440 SCV002775418 uncertain significance Aortic aneurysm, familial thoracic 4; Visceral myopathy 2; Megacystis-microcolon-intestinal hypoperistalsis syndrome 2 2021-08-23 criteria provided, single submitter clinical testing

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