Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000641707 | SCV000763355 | pathogenic | Hemochromatosis type 4 | 2022-07-23 | criteria provided, single submitter | clinical testing | 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: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 56158). This missense change has been observed in individuals with hemochromatosis (PMID: 21199650, 31640930). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs387907377, gnomAD 0.006%). This sequence change replaces glycine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 204 of the SLC40A1 protein (p.Gly204Ser). Experimental studies have shown that this missense change affects SLC40A1 function (PMID: 23943237). For these reasons, this variant has been classified as Pathogenic. |
Fulgent Genetics, |
RCV000641707 | SCV000894249 | likely pathogenic | Hemochromatosis type 4 | 2018-10-31 | criteria provided, single submitter | clinical testing | |
Laboratory of Molecular Genetics and Genomics, |
RCV000641707 | SCV001445849 | likely pathogenic | Hemochromatosis type 4 | 2020-07-01 | criteria provided, single submitter | clinical testing | Identified in 15 patients harbouring clinical and biochemical symptomes of type 4 haemochromatosis |
DASA | RCV000641707 | SCV002318955 | pathogenic | Hemochromatosis type 4 | 2022-03-25 | criteria provided, single submitter | clinical testing | Well-established in vitro or in vivo functional studies supportive of a damaging effect on the gene or gene product (PMID: 23943237) - PS3_moderate. The c.610G>A;p.(Gly204Ser) missense change has been observed in affected individual(s) and ClinVar contains an entry for this variant (ClinVar ID: 56158; PMID: 23943237; PMID: 21199650; PMID: 21411349)-PS4. The variant is located in a mutational hot spot and/or critical and well-established functional domain (FPN1) - PM1. The variant is present at low allele frequencies population databases (rs387907377 – gnomAD 0.00007955%; ABraOM 0.000427 frequency - http://abraom.ib.usp.br.) - PM2_supporting. Multiple lines of computational evidence support a deleterious effect on the gene or gene product - PP3. In summary, the currently available evidence indicates that the variant is pathogenic |
Laboratoire de Génétique Moléculaire, |
RCV000049568 | SCV000082626 | not provided | not provided | no assertion provided | not provided |