ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.4016G>A (p.Arg1339His) (rs374271463)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000182515 SCV000234861 uncertain significance not provided 2013-10-31 criteria provided, single submitter clinical testing p.Arg1339His (R1339H) CGC>CAC: c.4016 G>A in exon 30 of the MYH11 gene (NM_002474.2).The Arg1339His variant in the MYH11 gene has not been reported as a disease-causing mutation or as a benign polymorphism to our knowledge. Although, Arg1339His results in a conservative amino acid substitution of one positively charged amino acid for another; this position is well conserved across species. In silico analysis predicts Arg1339His is probably damaging to the protein structure/function. The Arg1339His variant was not observed with any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. However, no mutations in nearby residues have been reported in association with TAAD, indicating this region of the protein may be tolerant of change. With the clinical and molecular information available at this time, we cannot definitively determine if Arg1339His is a disease-causing mutation or a rare benign variant. The variant is found in TAAD panel(s).
Illumina Clinical Services Laboratory,Illumina RCV000699160 SCV000395285 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). 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.
Illumina Clinical Services Laboratory,Illumina RCV000288562 SCV000395286 uncertain significance Lissencephaly, Recessive 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000699160 SCV000827858 uncertain significance Aortic aneurysm, familial thoracic 4 2018-07-03 criteria provided, single submitter clinical testing This sequence change replaces arginine with histidine at codon 1346 of the MYH11 protein (p.Arg1346His). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and histidine. This variant is present in population databases (rs374271463, ExAC 0.007%). This variant has not been reported in the literature in individuals with MYH11-related disease. ClinVar contains an entry for this variant (Variation ID: 201071). 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Fulgent Genetics,Fulgent Genetics RCV000699160 SCV000896506 uncertain significance Aortic aneurysm, familial thoracic 4 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001121346 SCV001279940 uncertain significance Lissencephaly 4 2018-01-13 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.
Color RCV001192184 SCV001360185 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-09-15 criteria provided, single submitter clinical testing

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