ClinVar Miner

Submissions for variant NM_000064.4(C3):c.26T>C (p.Leu9Pro)

gnomAD frequency: 0.00053  dbSNP: rs138214338
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV001092937 SCV001249684 uncertain significance not provided 2019-09-01 criteria provided, single submitter clinical testing
Illumina Laboratory Services, Illumina RCV001133672 SCV001293381 benign Atypical hemolytic-uremic syndrome with C3 anomaly 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina RCV001133673 SCV001293382 uncertain significance Age related macular degeneration 9 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV001133674 SCV001293383 uncertain significance Complement component 3 deficiency 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Labcorp Genetics (formerly Invitae), Labcorp RCV001092937 SCV002294569 uncertain significance not provided 2025-02-02 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with proline, which is neutral and non-polar, at codon 9 of the C3 protein (p.Leu9Pro). This variant is present in population databases (rs138214338, gnomAD 0.08%). This missense change has been observed in individual(s) with C3-related conditions (PMID: 29670616, 29888403, 34631043, 35295324). ClinVar contains an entry for this variant (Variation ID: 872465). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002294438 SCV002587677 uncertain significance Atypical hemolytic-uremic syndrome 2021-01-22 criteria provided, single submitter clinical testing
Mayo Clinic Laboratories, Mayo Clinic RCV001092937 SCV004224545 uncertain significance not provided 2023-03-29 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005021439 SCV005648801 uncertain significance Age related macular degeneration 9; Atypical hemolytic-uremic syndrome with C3 anomaly; Complement component 3 deficiency 2024-04-10 criteria provided, single submitter clinical testing

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