Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000505776 | SCV000207863 | uncertain significance | not provided | 2017-06-05 | criteria provided, single submitter | clinical testing | The R169Q variant has not been published in association with the Noonan syndrome spectrum to our knowledge; the variant has been observed as a germline variant in an individual with lung cancer but no reported other phenotype (Marks et al., 2007). It was observed to co-occur with the M269T pathogenic variant in the SOS1 gene in a patient at GeneDx. The variant is observed in 1/10172 (0.01%) alleles from individuals of African background in the ExAC dataset (Lek et al., 2016). R169Q is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species; however, in silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Labcorp Genetics |
RCV000463046 | SCV000550344 | uncertain significance | Costello syndrome | 2023-10-14 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 169 of the HRAS protein (p.Arg169Gln). This variant is present in population databases (rs142218590, gnomAD 0.01%). This missense change has been observed in individual(s) with an unspecified cancer (PMID: 25742471). ClinVar contains an entry for this variant (Variation ID: 180856). 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. |
Baylor Genetics | RCV000463046 | SCV001481324 | uncertain significance | Costello syndrome | 2019-07-31 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Sema4, |
RCV002258816 | SCV002537986 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-01-10 | criteria provided, single submitter | curation | |
Fulgent Genetics, |
RCV002492617 | SCV002800805 | uncertain significance | Large congenital melanocytic nevus; Linear nevus sebaceous syndrome; Malignant tumor of urinary bladder; Costello syndrome; Epidermal nevus; Thyroid cancer, nonmedullary, 2 | 2021-09-28 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003390855 | SCV004119909 | uncertain significance | HRAS-related disorder | 2023-02-16 | criteria provided, single submitter | clinical testing | The HRAS c.506G>A variant is predicted to result in the amino acid substitution p.Arg169Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.016% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/11-532700-C-T) and is interpreted as uncertain in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/180856/). Although we suspect this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |