Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001936954 | SCV002225979 | uncertain significance | not provided | 2022-06-27 | criteria provided, single submitter | clinical testing | This sequence change replaces isoleucine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 400 of the ANLN protein (p.Ile400Val). 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. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The valine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. This variant has not been reported in the literature in individuals affected with ANLN-related conditions. This variant is present in population databases (rs780364655, gnomAD 0.03%). |
Ambry Genetics | RCV004043117 | SCV003579567 | uncertain significance | not specified | 2021-10-12 | criteria provided, single submitter | clinical testing | The c.1198A>G (p.I400V) alteration is located in exon 6 (coding exon 6) of the ANLN gene. This alteration results from a A to G substitution at nucleotide position 1198, causing the isoleucine (I) at amino acid position 400 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Clinical Genomics Laboratory, |
RCV004558752 | SCV005047104 | uncertain significance | Focal segmental glomerulosclerosis 8 | 2024-04-08 | criteria provided, single submitter | clinical testing | The ANLN c. 1198A>G (p.Ile400Val) variant, to our knowledge, has not been reported in the medical literature in relation to renal disease. This variant is observed on 9/282,768 alleles in the general population (gnomAD v2.1.1). This variant has been reported in the ClinVar database as a variant of uncertain significance by two submitters (ClinVar ID: 1440732). Computational predictors suggest that the variant does not impact ANLN function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time. |