Total submissions: 7
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000442662 | SCV000532355 | uncertain significance | not provided | 2016-09-30 | criteria provided, single submitter | clinical testing | The R954H variant in the C3 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The R954H variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R954H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret R954H as a variant of uncertain significance. |
Illumina Laboratory Services, |
RCV001136338 | SCV001296167 | uncertain significance | Complement component 3 deficiency | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Laboratory Services, |
RCV001136339 | SCV001296168 | benign | Atypical hemolytic-uremic syndrome with C3 anomaly | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. |
Illumina Laboratory Services, |
RCV001136341 | SCV001296170 | uncertain significance | Age related macular degeneration 9 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Invitae | RCV000442662 | SCV002384538 | likely benign | not provided | 2023-08-16 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003418134 | SCV004118422 | uncertain significance | C3-related condition | 2022-09-19 | criteria provided, single submitter | clinical testing | The C3 c.2861G>A variant is predicted to result in the amino acid substitution p.Arg954His. This variant has been identified in an individual with atypical hemolytic uremic syndrome (Supplementary Table 1 and 3, Thergaonkar et al. 2018. PubMed ID: 28939980). This variant is reported in 0.15% of alleles in individuals of Ashkenazi Jewish descent in gnomAD and is reported in the homozygous state in one individual of South Asian descent, which may be too common to be causative (http://gnomad.broadinstitute.org/variant/19-6696606-C-T). Although we suspect that this variant may be benign, at this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Mayo Clinic Laboratories, |
RCV000442662 | SCV004224535 | uncertain significance | not provided | 2022-02-04 | criteria provided, single submitter | clinical testing | BP4 |