Submissions for variant NM_000330.4(RS1):c.187T>C (p.Cys63Arg)

dbSNP: rs2147194234

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV002021381	SCV002311129	uncertain significance	not provided	2021-06-11	criteria provided, single submitter	clinical testing	This variant has been observed in individual(s) with clinical features of retinoschisis (PMID: 31106028, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change replaces cysteine with arginine at codon 63 of the RS1 protein (p.Cys63Arg). The cysteine residue is highly conserved and there is a large physicochemical difference between cysteine and arginine. 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. This variant disrupts the p.Cys63 amino acid residue in RS1. Other variant(s) that disrupt this residue have been observed in individuals with RS1-related conditions (PMID: 29739629), which suggests that this may be a clinically significant amino acid residue. 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 disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre	RCV003987958	SCV004805120	likely pathogenic	Juvenile retinoschisis	2024-03-17	criteria provided, single submitter	research