Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000305177 | SCV000428096 | uncertain significance | Alport syndrome | 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. |
| Fulgent Genetics, |
RCV005003640 | SCV002792104 | uncertain significance | Autosomal recessive Alport syndrome; Hematuria, benign familial, 1 | 2024-06-18 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV002521410 | SCV003453221 | likely benign | not provided | 2024-04-08 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002521411 | SCV003714774 | uncertain significance | Inborn genetic diseases | 2022-11-21 | criteria provided, single submitter | clinical testing | The c.2516C>T (p.P839L) alteration is located in exon 29 (coding exon 28) of the COL4A4 gene. This alteration results from a C to T substitution at nucleotide position 2516, causing the proline (P) at amino acid position 839 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Victorian Clinical Genetics Services, |
RCV000305177 | SCV005398178 | uncertain significance | Alport syndrome | 2022-02-02 | criteria provided, single submitter | clinical testing | Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as VUS-3B. Following criteria are met: 0102 - Loss of function is a known mechanism of disease for this gene and is associated with COL4A4-related nephropathy. Dominant negative is a suspected mechanism of disease for this gene as it is a structural protein (PMIDs: 12028435, 24046192). (I) 0108 - This gene is associated with both recessive and dominant disease. Alport syndrome typically has biallelic inheritance, although rare cases of monoallelic inheritance have been reported and has been associated with a milder phenotype and later onset (PMID: 28704582). TBMN and focal segmental glomerulosclerosis (FSGS) are associated with autosomal dominant inheritance (OMIM, PMIDs: 16467446, 17942953). (I) 0200 - Variant is predicted to result in a missense amino acid change from proline to leucine. (I) 0251 - This variant is heterozygous. (I) 0304 - Variant is present in gnomAD <0.01 (v2: 8 heterozygotes, 0 homozygotes). (SP) 0502 - Missense variant with conflicting in silico predictions and uninformative conservation. (I) 0600 - Variant is located in the annotated triple helix domain. Specifically, it is the X of the G-X-Y repeat (Uniprot, NCBI). (I) 0705 - No comparable missense variants have previous evidence for pathogenicity. (I) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1208 - Inheritance information for this variant is not currently available in this individual. (I) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign |