Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Athena Diagnostics | RCV000991624 | SCV001143241 | uncertain significance | not provided | 2020-09-01 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001140737 | SCV001301023 | 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. |
Gene |
RCV000991624 | SCV002043949 | uncertain significance | not provided | 2021-06-22 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 27535533, 30647093, 31408864) |
Myriad Genetics, |
RCV000859980 | SCV002060099 | uncertain significance | Autosomal recessive Alport syndrome | 2021-11-10 | criteria provided, single submitter | clinical testing | NM_000092.4(COL4A4):c.4708G>A(E1570K) is a missense variant classified as a variant of uncertain significance in the context of COL4A4-related Alport syndrome. E1570K has been observed in cases with relevant disease (PMID: 31408864, Sanchez_2018_(no PMID; abstract)). Functional assessments of this variant are not available in the literature. E1570K has been observed in population frequency databases (gnomAD: SAS 0.02%). In summary, there is insufficient evidence to classify NM_000092.4(COL4A4):c.4708G>A(E1570K) as pathogenic or benign. Please note: this variant was assessed in the context of healthy population screening. |
Fulgent Genetics, |
RCV005004417 | SCV002779900 | uncertain significance | Autosomal recessive Alport syndrome; Hematuria, benign familial, 1 | 2024-05-21 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV000991624 | SCV003439670 | uncertain significance | not provided | 2021-10-28 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 1570 of the COL4A4 protein (p.Glu1570Lys). This variant is present in population databases (rs757328549, gnomAD 0.02%). This missense change has been observed in individual(s) with COL4A4-related conditions (PMID: 30647093). ClinVar contains an entry for this variant (Variation ID: 634650). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Not Available"; Align-GVGD: "Class C0"). 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. |
Division of Nephrology, |
RCV000859980 | SCV000920872 | likely pathogenic | Autosomal recessive Alport syndrome | no assertion criteria provided | provider interpretation | The c.4708G>A variant in COL4A4 was observed along with another COL4A4 variant, c.3861delinsCTC, in a female patient with clinical and renal biopsy findings consistent with Alport Syndrome. This patient was interpreted as being compound heterozygous for variants causing autosomal recessive Alport Syndrome. This patient had a relatively mild phenotype. This case manuscript is under revision for publication. | |
Natera, |
RCV001140737 | SCV001459913 | uncertain significance | Alport syndrome | 2020-09-16 | no assertion criteria provided | clinical testing |