Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001204909 | SCV001376138 | uncertain significance | Costello syndrome | 2023-11-12 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 142 of the HRAS protein (p.Ile142Met). This variant is present in population databases (rs533567288, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with HRAS-related conditions. ClinVar contains an entry for this variant (Variation ID: 936167). Advanced modeling performed at Invitae incorporating data from internal and/or published experimental studies (Invitae) indicates that this missense variant is not expected to disrupt HRAS 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. |
Ambry Genetics | RCV002327468 | SCV002631702 | uncertain significance | Cardiovascular phenotype | 2021-08-19 | criteria provided, single submitter | clinical testing | The p.I142M variant (also known as c.426C>G), located in coding exon 3 of the HRAS gene, results from a C to G substitution at nucleotide position 426. The isoleucine at codon 142 is replaced by methionine, an amino acid with highly similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |