Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Molecular Biology Laboratory, |
RCV001281287 | SCV001425017 | likely pathogenic | Benign familial hematuria | 2020-02-01 | criteria provided, single submitter | research | |
Fulgent Genetics, |
RCV002480863 | SCV002781600 | likely pathogenic | Autosomal recessive Alport syndrome; Benign familial hematuria | 2022-05-11 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV003399024 | SCV004118967 | likely pathogenic | COL4A4-related condition | 2022-12-19 | criteria provided, single submitter | clinical testing | The COL4A4 c.193G>A variant is predicted to result in the amino acid substitution p.Gly65Ser. This variant was reported with another Gly substitution variant in the COL4A3 gene a patient with Alport syndrome and suggested digenic inheritance (P194 in Domingo-Gallego A et al 2022. PubMed ID: 33532864). The Gly65 variant affects a Gly residue of the conserved triple helical domain (residues 65 – 1459) of the COL4A4 protein (uniprot.org). The majority of pathogenic variants in COL4A4 substitute a glycine residue to a bulkier amino acid in the triple-helical domain (Hudson et al. 1993. PubMed ID: 8253711; https://www.ncbi.nlm.nih.gov/books/NBK1207/). This variant is reported in 0.012% of alleles in individuals of Latino descent in gnomAD (http://gnomad.broadinstitute.org/variant/2-227985864-C-T). The c.193G>A variant is interpreted as likely pathogenic for autosomal recessive COL4A4-related disorders. |