Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002766250 | SCV003021354 | uncertain significance | not provided | 2022-04-23 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 3915 of the HMCN1 protein (p.Val3915Ile). This variant is present in population databases (rs201008146, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with HMCN1-related conditions. 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 isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Ambry Genetics | RCV004067916 | SCV003940829 | uncertain significance | not specified | 2023-05-09 | criteria provided, single submitter | clinical testing | The c.11743G>A (p.V3915I) alteration is located in exon 77 (coding exon 77) of the HMCN1 gene. This alteration results from a G to A substitution at nucleotide position 11743, causing the valine (V) at amino acid position 3915 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Genome- |
RCV003455569 | SCV004179887 | uncertain significance | Age related macular degeneration 1 | 2023-04-11 | criteria provided, single submitter | clinical testing |