Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Fulgent Genetics, |
RCV000477802 | SCV000893418 | pathogenic | Familial hypokalemia-hypomagnesemia | 2022-05-10 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000681947 | SCV000932032 | pathogenic | not provided | 2024-01-31 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 964 of the SLC12A3 protein (p.Arg964Gln). This variant is present in population databases (rs202114767, gnomAD 0.2%). This missense change has been observed in individuals with Gitelman syndrome (PMID: 8528245, 17654016, 21415153, 22214629, 30596175). It has also been observed to segregate with disease in related individuals. This variant is also known as p.Arg955Gln. ClinVar contains an entry for this variant (Variation ID: 417864). 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 expected to disrupt SLC12A3 protein function with a positive predictive value of 95%. Experimental studies have shown that this missense change affects SLC12A3 function (PMID: 12039972). For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV000681947 | SCV001826237 | likely pathogenic | not provided | 2023-05-31 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 12039972, 8528245, 21415153, 15206555, 18391953, 31589614, 22214629, 35327948, 17654016, 19508680, 30596175, 33348466, 35785516, Yanan2023[noPMID], 22009145) |
Athena Diagnostics Inc | RCV000681947 | SCV001879514 | pathogenic | not provided | 2020-12-15 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). Assessment of experimental evidence suggests this variant results in abnormal protein function. Study showed this variant to significantly reduce sodium uptake compared to wild-type (PMID: 12039972). In multiple individuals, this variant has been seen with a single recessive pathogenic variant in the same gene, suggesting this variant may also be pathogenic. |
Genome- |
RCV000477802 | SCV002055355 | likely pathogenic | Familial hypokalemia-hypomagnesemia | 2021-07-15 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV002525742 | SCV003755755 | pathogenic | Inborn genetic diseases | 2020-11-05 | criteria provided, single submitter | clinical testing | The c.2891G>A (p.R964Q) alteration is located in exon 25 (coding exon 25) of the SLC12A3 gene. This alteration results from a G to A substitution at nucleotide position 2891, causing the arginine (R) at amino acid position 964 to be replaced by a glutamine (Q). Based on data from the Genome Aggregation Database (gnomAD) database, the SLC12A3 c.2891G>A alteration was observed in 0.01% (41/282888) of total alleles studied, with a frequency of 0.17% (18/10370) in the Ashkenazi Jewish subpopulation. This alteration has been reported in multiple patients with Gitelman syndrome in both the homozygous and compound heterozygous states (Enya, 2004; Fava, 2007; Nakamura, 2010; Vargas-Poussou, 2011; Glaudemans, 2012; Ito, 2012; Fujimura, 2019). This amino acid position is well conserved in available vertebrate species. The in silico prediction for the p.R964Q alteration is inconclusive. Based on the available evidence, this alteration is classified as pathogenic. |
Ce |
RCV000681947 | SCV004033492 | pathogenic | not provided | 2023-08-01 | criteria provided, single submitter | clinical testing | SLC12A3: PM3:Very Strong, PM2, PM5, PS3:Supporting, BP4 |
Revvity Omics, |
RCV000477802 | SCV004238359 | pathogenic | Familial hypokalemia-hypomagnesemia | 2023-05-19 | criteria provided, single submitter | clinical testing | |
Division of Human Genetics, |
RCV000477802 | SCV000536717 | pathogenic | Familial hypokalemia-hypomagnesemia | 2015-09-23 | no assertion criteria provided | research | |
Gharavi Laboratory, |
RCV000681947 | SCV000809435 | likely pathogenic | not provided | 2018-09-16 | no assertion criteria provided | research |