Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV001002460 | SCV001160403 | uncertain significance | Retinitis pigmentosa 38 | 2019-04-09 | criteria provided, single submitter | clinical testing | The MERTK c.2165G>A; p.Arg722Gln variant (rs147779020), to our knowledge, is not reported in the medical literature or gene-specific databases. This variant is found on only four chromosomes (4/282854 alleles) in the Genome Aggregation Database, indicating it is not a common polymorphism. The arginine at codon 722 is highly conserved, it occurs close to the catalytic site of the MERTK kinase domain (Huang 2009), and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. However, given the lack of clinical and functional data, the significance of the p.Arg722Gln variant is uncertain at this time. References: Huang X et al. Structural insights into the inhibited states of the Mer receptor tyrosine kinase. J Struct Biol. 2009 Feb;165(2):88-96. |
| Labcorp Genetics |
RCV001234343 | SCV001406983 | uncertain significance | not provided | 2023-12-04 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 722 of the MERTK protein (p.Arg722Gln). This variant is present in population databases (rs147779020, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with MERTK-related conditions. ClinVar contains an entry for this variant (Variation ID: 811947). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt MERTK protein function with a positive predictive value of 80%. 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. |
| Genomic Medicine Center of Excellence, |
RCV001002460 | SCV004809384 | uncertain significance | Retinitis pigmentosa 38 | 2024-04-04 | criteria provided, single submitter | clinical testing |