Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000700764 | SCV000829535 | uncertain significance | MEGF8-related Carpenter syndrome | 2022-06-07 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 750 of the MEGF8 protein (p.His750Arg). This variant is present in population databases (rs151116615, gnomAD 0.2%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with MEGF8-related conditions. ClinVar contains an entry for this variant (Variation ID: 577904). 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 tolerated. 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. |
Baylor Genetics | RCV000700764 | SCV001524091 | uncertain significance | MEGF8-related Carpenter syndrome | 2020-01-27 | criteria provided, single submitter | clinical testing | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. |
Ambry Genetics | RCV002534386 | SCV003693671 | uncertain significance | Inborn genetic diseases | 2022-10-26 | criteria provided, single submitter | clinical testing | The c.2249A>G (p.H750R) alteration is located in exon 13 (coding exon 13) of the MEGF8 gene. This alteration results from a A to G substitution at nucleotide position 2249, causing the histidine (H) at amino acid position 750 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Ce |
RCV003424295 | SCV004139610 | uncertain significance | not provided | 2023-06-01 | criteria provided, single submitter | clinical testing |