Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000598510 | SCV000709718 | uncertain significance | not specified | 2018-03-06 | criteria provided, single submitter | clinical testing | Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: GnomAd 11-534312-T-C: Europeans 7/126246;Change to Cys identified in microbat; Not in ClinVar, Pubmed, Google search or HGMD |
Labcorp Genetics |
RCV001322927 | SCV001513822 | uncertain significance | Costello syndrome | 2023-05-30 | criteria provided, single submitter | clinical testing | 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. 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 expected to disrupt HRAS protein function. ClinVar contains an entry for this variant (Variation ID: 503537). This variant has not been reported in the literature in individuals affected with HRAS-related conditions. This variant is present in population databases (rs764622691, gnomAD 0.006%). This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 4 of the HRAS protein (p.Tyr4Cys). |
Fulgent Genetics, |
RCV002483665 | SCV002792622 | uncertain significance | Large congenital melanocytic nevus; Linear nevus sebaceous syndrome; Malignant tumor of urinary bladder; Costello syndrome; Epidermal nevus; Thyroid cancer, nonmedullary, 2 | 2021-09-17 | criteria provided, single submitter | clinical testing | |
St. |
RCV001322927 | SCV004171443 | uncertain significance | Costello syndrome | 2023-09-20 | criteria provided, single submitter | clinical testing | The HRAS c.11A>G (p.Tyr4Cys) missense change has a maximum subpopulation frequency of 0.0055% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. 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. |