Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Baylor Genetics | RCV000680122 | SCV000807564 | uncertain significance | Autosomal recessive osteopetrosis 1 | 2017-09-01 | criteria provided, single submitter | clinical testing | Likely pathogenicity based on finding it once in our laboratory with a nonsense variant (R670X, phase unknown) in a 17-year-old male with intellectual disability, autism spectrum, dysmorphisms, macrocephaly, advance bone age, precocious puberty, possible hearing loss, ichthyosis (and STS deletion), frequent fractures with decreased bone density, joint laxity. |
| Invitae | RCV002531411 | SCV003522125 | uncertain significance | not provided | 2021-09-24 | criteria provided, single submitter | clinical testing | This sequence change replaces serine with leucine at codon 474 of the TCIRG1 protein (p.Ser474Leu). The serine residue is highly conserved and there is a large physicochemical difference between serine and leucine. This variant is present in population databases (rs199914625, ExAC 0.06%). This variant has not been reported in the literature in individuals with TCIRG1-related disease. 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. |