ClinVar Miner

Submissions for variant NM_002474.3(MYH11):c.5052C>G (p.Ser1684Arg)

dbSNP: rs760908992
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000202728 SCV000257760 uncertain significance Aortic aneurysm, familial thoracic 4 2015-03-06 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000757517 SCV000885771 uncertain significance not provided 2018-01-28 criteria provided, single submitter clinical testing The MYH11 c.5052C>G p.Ser1684Arg variant (rs760908992), to our knowledge, is not reported in the medical literature, gene specific variation databases, nor has it been previously identified by our laboratory. This variant is listed in the genome Aggregation Database (gnomAD) with an overall population frequency of 0.001% (identified on 3 out of 246,262 chromosomes). The serine at position 1684 is highly conserved considering 13 species (Alamut software v.2.10.0) and computational analyses of the effects of the p.Ser1684Arg variant on protein structure and function predict an effect (SIFT: damaging, MutationTaster: disease causing, PolyPhen-2: possibly damaging). Based on all the available evidence, the clinical significance of the p.Ser1684Arg variant cannot be determined with certainty.
Color Diagnostics, LLC DBA Color Health RCV001184303 SCV001350251 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-01-10 criteria provided, single submitter clinical testing This missense variant replaces serine with arginine at codon 1691 of the MYH11 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 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 4/251486 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.
Invitae RCV000202728 SCV002168994 uncertain significance Aortic aneurysm, familial thoracic 4 2024-01-28 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 1691 of the MYH11 protein (p.Ser1691Arg). This variant is present in population databases (rs760908992, gnomAD 0.003%). 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: 218495). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt MYH11 protein function with a negative predictive value of 95%. 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.
New York Genome Center RCV003448286 SCV004176181 uncertain significance Aortic aneurysm, familial thoracic 4; Visceral myopathy 2 2023-05-10 criteria provided, single submitter clinical testing

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