Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001837967 | SCV000659259 | uncertain significance | Hypercholesterolemia, autosomal dominant, type B; Familial hypobetalipoproteinemia 1 | 2021-08-28 | criteria provided, single submitter | clinical testing | This sequence change replaces valine with methionine at codon 4074 of the APOB protein (p.Val4074Met). The valine residue is moderately conserved and there is a small physicochemical difference between valine and methionine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with APOB-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Ambry Genetics | RCV002527953 | SCV003659651 | uncertain significance | Inborn genetic diseases | 2022-11-07 | criteria provided, single submitter | clinical testing | The c.12220G>A (p.V4074M) alteration is located in exon 29 (coding exon 29) of the APOB gene. This alteration results from a G to A substitution at nucleotide position 12220, causing the valine (V) at amino acid position 4074 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |