Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000798562 | SCV000938183 | likely pathogenic | Melnick-Fraser syndrome | 2019-03-13 | criteria provided, single submitter | clinical testing | This variant has been observed to be de novo in an individual with clinical features of branchio-oto-renal syndrome (BORS) (Invitae). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with arginine at codon 580 of the EYA1 protein (p.Leu580Arg). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and arginine. |