Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001081751 | SCV000638957 | benign | Familial hemophagocytic lymphohistiocytosis 3 | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000762001 | SCV000892236 | likely benign | not provided | 2024-03-01 | criteria provided, single submitter | clinical testing | UNC13D: BP4 |
Mendelics | RCV000762001 | SCV001135104 | likely benign | not provided | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Illumina Laboratory Services, |
RCV001081751 | SCV001285894 | uncertain significance | Familial hemophagocytic lymphohistiocytosis 3 | 2017-04-27 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Gene |
RCV000762001 | SCV001769981 | uncertain significance | not provided | 2020-03-23 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant does not alter protein structure/function; Has been previously reported in cis with I848L in unrelated patients who had features of macrophage activation syndrome and autoimmune lymphoproliferative syndrome (Zhang et al., 2008; Arico et al., 2013; Kernan et al., 2018).; Transfection study of the I848L and A995P variants showed that these variants, both alone and in combination, decreased granule exocytosis when compared to wild type (Arico et al., 2013); This variant is associated with the following publications: (PMID: 33408077, 29977033, 18759271, 23840885, 29864493) |
Genetic Services Laboratory, |
RCV001821541 | SCV002070063 | uncertain significance | not specified | 2021-08-11 | criteria provided, single submitter | clinical testing | The sequence change, c.2983G>C, in exon 31 results in an amino acid change, p.Ala995Pro. This sequence change has been previously described in one individual with autoimmune lymphoproliferative syndrome (PMID: 23840885), one individual with extreme hyperferritinemia (PMID: 29977033), and one individual with juvenile idiopathic arthritis (PMID: 33408077). This sequence change has been described in the gnomAD database with a low frequency of 0.27% in Ashkenazi Jewish subpopulation (dbSNP rs138760432). The p.Ala995Pro change affects a poorly conserved amino acid residue located in a domain of the UNC13D protein that is known to be functional. The p.Ala995Pro substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). Functional studies show p.Ala995Pro is a loss-of-function variant (PMID: 23840885). Due to the lack of sufficient evidence, the clinical significance of the p.Ala995Pro change remains unknown at this time. |
Genome Diagnostics Laboratory, |
RCV002263769 | SCV002543177 | uncertain significance | Autoinflammatory syndrome | 2017-10-02 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV001081751 | SCV003828028 | uncertain significance | Familial hemophagocytic lymphohistiocytosis 3 | 2020-02-28 | criteria provided, single submitter | clinical testing | |
Diagnostic Laboratory, |
RCV000762001 | SCV001744520 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Genome Diagnostics Laboratory, |
RCV000762001 | SCV001928903 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000762001 | SCV001969571 | likely benign | not provided | no assertion criteria provided | clinical testing |