Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000156408 | SCV000206126 | uncertain significance | not specified | 2014-07-31 | criteria provided, single submitter | clinical testing | A whole gene gain of HRAS was identified in one individual with fetal hydrops, w hich was inherited from an unaffected parent (LMM unpublished). It is unknown if that gain extended beyond the HRAS gene. Additionally, copy number gains of a r egion encompassing HRAS and 12 other genes have been reported in 3 individuals w ith congenital heart defects (1 individual with coarctation of aorta who had Tur ner syndrome, 1 individual with double inlet left ventricle, and 1 individual wi th subaortic stenosis). These copy number gains have not been identified in 5812 control individuals (Tomita-Mitchell, 2012). The exact breakpoints of this HRAS whole gene duplication are not known and the duplication may extend well beyond the HRAS gene. Gain of function in HRAS is an established disease mechanism for Costello syndrome, though the functional impact of a whole gene duplication rem ains unclear. In summary, the clinical significance of this duplication is uncer tain. |
Labcorp Genetics |
RCV000461310 | SCV000563972 | uncertain significance | Costello syndrome | 2016-10-16 | criteria provided, single submitter | clinical testing | A gross duplication of the genomic region encompassing the full coding sequence of the HRAS gene has been identified. The boundaries of this event are unknown as the duplication extends beyond the assayed region for this gene and therefore may encompass additional genes. As the precise location of this duplication is unknown, it may be in tandem or it may be located elsewhere in the genome. Whole gene duplications of HRAS have not been reported in the literature in individuals with a HRAS-related disease. In summary, the exact genomic location of this variant is unknown and the impact of this duplication on HRAS protein function has not been established. Therefore, it has been classified as a Variant of Uncertain Significance. |