Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV002034865 | SCV002107360 | uncertain significance | not provided | 2024-02-14 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function |
Ambry Genetics | RCV002334721 | SCV002642532 | uncertain significance | Familial thoracic aortic aneurysm and aortic dissection | 2021-07-08 | criteria provided, single submitter | clinical testing | The p.R1703C variant (also known as c.5107C>T), located in coding exon 35 of the MYH11 gene, results from a C to T substitution at nucleotide position 5107. The arginine at codon 1703 is replaced by cysteine, an amino acid with highly dissimilar 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. |
Labcorp Genetics |
RCV002543441 | SCV003515358 | uncertain significance | Aortic aneurysm, familial thoracic 4 | 2024-12-05 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 1710 of the MYH11 protein (p.Arg1710Cys). This variant is present in population databases (rs201108170, gnomAD 0.04%). 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: 1345011). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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. |
ARUP Laboratories, |
RCV002034865 | SCV005876149 | uncertain significance | not provided | 2024-11-26 | criteria provided, single submitter | clinical testing | The MYH11 c.5107C>T; p.Arg1703Cys variant (rs201108170), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 1345011). This variant is found in the African population with an allele frequency of 0.044% (11/24,958 alleles) in the Genome Aggregation Database (v2.1.1). Computational analyses are uncertain whether this variant is neutral or deleterious (REVEL: 0.511). Given the lack of clinical and functional data, the significance of this variant is uncertain at this time. |