Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
ARUP Laboratories, |
RCV001001044 | SCV001158163 | likely pathogenic | Retinitis pigmentosa 38 | 2019-02-15 | criteria provided, single submitter | clinical testing | The MERTK c.2162A>C; p.His721Pro variant (rs778005207), to our knowledge, is not reported in the medical literature or gene-specific databases. In testing performed at ARUP Laboratories, this variant was detected in two relatives with juvenile macular degeneration in trans to a full-gene MERTK deletion. The p.His721Pro variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism. The histidine at codon 721 is highly conserved, it occurs in a functionally important tyrosine kinase domain, and computational analyses (SIFT, PolyPhen-2) predict that this variant is deleterious. Additionally, another variant at this codon (p.His721Gln) is reported in the homozygous state in an individual with rod-cone dystrophy and is considered disease-causing (Audo 2018). Based on available information, the p.His721Pro variant is considered to be likely pathogenic. References: Audo I et al. MERTK mutation update in inherited retinal diseases. Hum Mutat. 2018 Jul;39(7):887-913. |