Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000697569 | SCV000826188 | uncertain significance | CHARGE syndrome | 2022-12-02 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 500 of the SEMA3E protein (p.Arg500Trp). This variant is present in population databases (rs111300014, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with SEMA3E-related conditions. ClinVar contains an entry for this variant (Variation ID: 575377). 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. |
Gene |
RCV001813799 | SCV002061012 | uncertain significance | not provided | 2022-01-11 | criteria provided, single submitter | clinical testing | Observed in a proband with Kallman syndrome, congenital hypogonadotrophic hypogonadism, cryptorchidism, azoospermia, olfactory nerve center maldevelopment, and vitiligo, but familial segregation information was not included (Zhang et al., 2021); Observed in a proband with pituitary stalk interruption syndrome with decreased growth rate, deficiency of thyrotropin, Fanconi syndrome, microphthalmia, and cryptorchidism, but familial segregation information was not included and the proband was reported to have potentially causative variants in other genes (Brauner et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34348883, 33270637) |
Fulgent Genetics, |
RCV002485702 | SCV002778465 | uncertain significance | CHARGE syndrome; Hypogonadotropic hypogonadism 7 with or without anosmia | 2022-05-11 | criteria provided, single submitter | clinical testing | |
Clinical Genetics Laboratory, |
RCV001813799 | SCV005198207 | uncertain significance | not provided | 2022-06-30 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV004745555 | SCV005359047 | uncertain significance | SEMA3E-related disorder | 2024-04-17 | no assertion criteria provided | clinical testing | The SEMA3E c.1498C>T variant is predicted to result in the amino acid substitution p.Arg500Trp. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.022% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |