Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
MAGI'S LAB - |
RCV000721116 | SCV000747189 | likely pathogenic | Oguchi disease | 2018-05-09 | criteria provided, single submitter | clinical testing | The p.(Ser133Leu) in SAG was identified in homozygous state in a male patient affected by Oguchi disease type 1. His parents are relatives. Application of ACMG guidelines: PM1, it's in a functional domain; PM2, absent from controls (or at extremely low frequency if recessive) in Exome Sequencing Project, 1000 Genomes Project, or Exome Aggregation Consortium; PP3, multiple lines of computational evidence support a deleterious effect on the gene or gene product (conservation, evolutionary, splicing impact, etc.): PP4, the patient's phenotype is specific for mutations in this gene. In summary, the p.(Ser133Leu) has been classified as likely pathogenic according to ACMG guidelines. |
Labcorp Genetics |
RCV001317376 | SCV001508035 | uncertain significance | not provided | 2020-06-16 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with leucine at codon 133 of the SAG protein (p.Ser133Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individual(s) with Oguchi disease (PMID: 30267901). ClinVar contains an entry for this variant (Variation ID: 559444). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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. |