ClinVar Miner

Submissions for variant NM_014585.6(SLC40A1):c.610G>A (p.Gly204Ser)

gnomAD frequency: 0.00001  dbSNP: rs387907377
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp 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, Fulgent Genetics RCV000641707 SCV000894249 likely pathogenic Hemochromatosis type 4 2018-10-31 criteria provided, single submitter clinical testing
Laboratory of Molecular Genetics and Genomics, Rennes University Hospital 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, CHU Pontchaillou RCV000049568 SCV000082626 not provided not provided no assertion provided not provided

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