Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000157922 | SCV000207857 | uncertain significance | not provided | 2019-01-03 | criteria provided, single submitter | clinical testing | Missense variants in this gene are often considered pathogenic (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |
Labcorp Genetics |
RCV000471505 | SCV000550348 | uncertain significance | Costello syndrome | 2024-01-25 | 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 123 of the HRAS protein (p.Arg123Cys). This variant is present in population databases (rs369106578, gnomAD 0.009%). 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: 180851). 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. |
Laboratory for Molecular Medicine, |
RCV000606057 | SCV000710906 | uncertain significance | not specified | 2017-06-20 | criteria provided, single submitter | clinical testing | The p.Arg123Cys variant in HRAS has not been previously reported in individuals with clinical features of Noonan syndrome disorders, but has been reported in Cl inVar by other clinical laboratories (VariationID: 180851). This variant has bee n identified in 3/33582 Latino chromosomes and 3/111670 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSN P rs369106578). Computational prediction tools and conservation analysis suggest that this variant may impact the protein, though this information is not predic tive enough to determine pathogenicity. In summary, the clinical significance o f the p.Arg123Cys variant is uncertain. |
Blueprint Genetics | RCV000157922 | SCV000927796 | uncertain significance | not provided | 2018-07-15 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000157922 | SCV001713547 | uncertain significance | not provided | 2020-09-04 | criteria provided, single submitter | clinical testing | |
St. |
RCV000471505 | SCV003928078 | uncertain significance | Costello syndrome | 2023-03-29 | criteria provided, single submitter | clinical testing | The HRAS c.367C>T (p.Arg123Cys) missense change has a maximum subpopulation frequency of 0.0086% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a deleterious effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in the literature in individuals with Costello syndrome. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. |
Fulgent Genetics, |
RCV005049434 | SCV005683778 | uncertain significance | Large congenital melanocytic nevus; Linear nevus sebaceous syndrome; Malignant tumor of urinary bladder; Costello syndrome; Epidermal nevus; Thyroid cancer, nonmedullary, 2 | 2024-01-06 | criteria provided, single submitter | clinical testing |