Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000616994 | SCV000731712 | uncertain significance | not specified | 2017-12-14 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Arg161His var iant in HRAS has been identified by our laboratory in 1 individual with clinical features of RASopathy; however the variant was inherited from an unaffected par ent. This variant has also been identified in 4/18840 East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org/; dbSN P rs748729430). Computational prediction tools and conservation analysis suggest that the p.Arg161His variant may impact the protein, though this information is not predictive enough to determine pathogenicity. In summary, while the clinica l significance of the p.Arg161His variant is uncertain, its identification in an unaffected individual suggests that it is more likely to be benign. ACMG/AMP cr iteria applied: BS2, PP3. |
Labcorp Genetics |
RCV001202259 | SCV001373366 | uncertain significance | Costello syndrome | 2023-10-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 161 of the HRAS protein (p.Arg161His). This variant is present in population databases (rs748729430, gnomAD 0.02%). 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: 517437). 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. 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. |