Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center for Genomics, |
RCV001281032 | SCV001468448 | uncertain significance | Complement component C1s deficiency; Ehlers-Danlos syndrome, periodontal type 2 | 2021-03-30 | criteria provided, single submitter | clinical testing | C1S NM_021442.3 exon 11 p.Glu400Gln (c.1198G>C): This variant has not been reported in the literature but is present in 0.07% (25/35428) of Latino alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/12-7175762-G-C?dataset=gnomad_r2_1). This variant amino acid Glutamine (Gln) is present in 4 species (Rhesus, Crab-eating Macaque, Green Monkey, Spiny softshell turtle) and is not well conserved among evolutionarily distant species; this suggests that this variant may not impact the protein. Additional computational prediction tools do not suggest an impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
| Labcorp Genetics |
RCV001871627 | SCV002127135 | uncertain significance | not provided | 2025-02-03 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with glutamine, which is neutral and polar, at codon 400 of the C1S protein (p.Glu400Gln). This variant is present in population databases (rs150549869, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with C1S-related conditions. ClinVar contains an entry for this variant (Variation ID: 992547). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
| Ambry Genetics | RCV002537912 | SCV003723156 | likely benign | Inborn genetic diseases | 2021-12-03 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |