Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000685257 | SCV000812732 | uncertain significance | Holoprosencephaly 9; Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome | 2018-06-20 | 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. 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. Family studies have indicated that an individual with holoprosencephaly inherited this variant from an unaffected parent, which suggests that this variant is not likely a primary cause of disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces leucine with proline at codon 238 of the GLI2 protein (p.Leu238Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. |