Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002004864 | SCV002235236 | uncertain significance | not provided | 2024-09-28 | criteria provided, single submitter | clinical testing | This sequence change replaces methionine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 1747 of the HMCN1 protein (p.Met1747Ile). This variant is present in population databases (rs766434071, gnomAD 0.006%). This missense change has been observed in individuals with clinical features of autosomal dominant inherited retinal dystrophy (internal data). ClinVar contains an entry for this variant (Variation ID: 1450506). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Probably Damaging". 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 | RCV004043960 | SCV003549390 | uncertain significance | not specified | 2021-09-01 | criteria provided, single submitter | clinical testing | The c.5241G>T (p.M1747I) alteration is located in exon 33 (coding exon 33) of the HMCN1 gene. This alteration results from a G to T substitution at nucleotide position 5241, causing the methionine (M) at amino acid position 1747 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
Genome- |
RCV003453841 | SCV004179784 | uncertain significance | Age related macular degeneration 1 | 2023-04-11 | criteria provided, single submitter | clinical testing |