Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000009380 | SCV000915706 | uncertain significance | Pseudohypoaldosteronism, type IB1, autosomal recessive | 2017-09-06 | criteria provided, single submitter | clinical testing | The SCNN1B c.109G>A (p.Gly37Ser) variant has been reported in one study and was found in a homozygous state in two male cousins, both affected with pseudohypoaldosteronism type I, from a large consanguineous family of Arabic ancestry (Chang et al. 1996). Both parents of both affected individuals were unaffected and carried the variant in a heterozygous state. The p.Gly37Ser variant is absent from 160 unrelated control alleles and is reported at a frequency of 0.000135 in the European (non-Finnish) population of the Genome Aggregation Database. Amiloride sensitive sodium ion currents measured by 2-electrode voltage clamp in oocytes expressing wild type or p.Gly37Ser variant in the beta subunit revealed that the oocytes with the variant had an approximately 60% reduction of sodium channel activity (Chang et al. 1996). The decrease in macroscopic sodium currents is suggested due to a decrease in channel open probability, which would explain the disease pathophysiology (Grunder et al. 1997; Kucher et al. 2011). Based on the limited clinical evidence, the p.Gly37Ser variant is considered to be of unknown significance but suspicious for pathogenicity for autosomal recessive pseudohypoaldosteronism type I. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Illumina Laboratory Services, |
RCV001120139 | SCV001278604 | benign | Bronchiectasis with or without elevated sweat chloride 1 | 2017-08-29 | 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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. |
| Illumina Laboratory Services, |
RCV001120417 | SCV001278901 | benign | Liddle syndrome 1 | 2017-08-29 | 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). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. |
| OMIM | RCV002310627 | SCV000029598 | pathogenic | Pseudohypoaldosteronism, type IB2, autosomal recessive | 1997-03-03 | no assertion criteria provided | literature only |