Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000551847 | SCV000652894 | uncertain significance | MEGF8-related Carpenter syndrome | 2016-06-17 | criteria provided, single submitter | clinical testing | This sequence change replaces leucine with tryptophan at codon 2619 of the MEGF8 protein (p.Leu2619Trp). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and tryptophan. While this variant is not present in population databases, the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in an individual with a MEGF8-related disease. In summary, this variant is a rare missense change with uncertain impact on protein function. It has been reported in both the population and affected individuals, but the available evidence is currently insufficient to determine its role 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 do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). |