Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000696019 | SCV000824562 | uncertain significance | Hereditary intrinsic factor deficiency | 2018-06-26 | 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. This variant has been observed in an individual affected with pancytopenia, B12 deficiency and homocystinuria (Invitae). This variant is present in population databases (rs767310648, ExAC 0.001%). This sequence change replaces phenylalanine with serine at codon 388 of the GIF protein (p.Phe388Ser). The phenylalanine residue is highly conserved and there is a large physicochemical difference between phenylalanine and serine. |