Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genomic Diagnostic Laboratory, |
RCV000239166 | SCV000297117 | pathogenic | not provided | 2015-10-30 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000239166 | SCV001501739 | pathogenic | not provided | 2020-10-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000239166 | SCV001784727 | pathogenic | not provided | 2020-08-18 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect; Xenopus and transfected cells showed that the potassium channel exhibits a higher activity and a higher calcium sensitivity compared with the wild-type channel (Rapetti-Mauss et al., 2015); This variant is associated with the following publications: (PMID: 32641076, 30577886, 26148990, 26198474, 26178367, 28496185, 27443288) |
Revvity Omics, |
RCV000412510 | SCV002023216 | pathogenic | Dehydrated hereditary stomatocytosis 2 | 2021-10-13 | criteria provided, single submitter | clinical testing | |
3billion | RCV000412510 | SCV002058976 | pathogenic | Dehydrated hereditary stomatocytosis 2 | 2022-01-03 | criteria provided, single submitter | clinical testing | Functional studies provide strong evidence of the variant having a damaging effect on the gene or gene product (PMID:26148990, PS3_S). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.889, PP3_P). A missense variant is a common mechanism associated with Dehydrated hereditary stomatocytosis 2 (PP2_P). It is observed at an extremely low frequency in the gnomAD v2.1.1 dataset (total allele frequency: 0.000000, PM2_M). Same nucleotide change resulting in same amino acid change has been previously reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000252601, PMID:26148990, PS1_S). Therefore, this variant is classified as pathogenic according to the recommendation of ACMG/AMP guideline. |
MGZ Medical Genetics Center | RCV000412510 | SCV002581315 | pathogenic | Dehydrated hereditary stomatocytosis 2 | 2022-06-20 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV000239166 | SCV004242966 | pathogenic | not provided | 2024-02-06 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000239166 | SCV004298406 | pathogenic | not provided | 2023-10-10 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 352 of the KCNN4 protein (p.Arg352His). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individuals with xerocytosis (PMID: 26148990, 26178367, 28496185). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 252601). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt KCNN4 protein function. Experimental studies have shown that this missense change affects KCNN4 function (PMID: 26148990). For these reasons, this variant has been classified as Pathogenic. |
OMIM | RCV000412510 | SCV000490257 | pathogenic | Dehydrated hereditary stomatocytosis 2 | 2015-12-11 | no assertion criteria provided | literature only |