Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Gene |
RCV000431545 | SCV000521070 | likely pathogenic | not provided | 2017-12-12 | criteria provided, single submitter | clinical testing | The I160T variant has been published previously in association with FSHR-related disorders (Binder et al., 2008; Beau et al., 1998). It has also been observed in the heterozygous state with no other FSHR variants in both affected individuals and controls (Binder et al., 2012). The variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. I160T is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position where amino acids with similar properties to Isoleucine are tolerated across species. In silico analysis predicts this variant is probably damaging to the protein structure/function. Additionally, functional studies have shown that I160T lowers FSH binding, cell surface expression, and activity of the FSHR protein compared to wild type (Beau et al., 1998). Therefore, we consider this variant to be likely pathogenic. |
| Illumina Laboratory Services, |
RCV000017631 | SCV001303557 | uncertain significance | Ovarian dysgenesis 1 | 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. |
| Illumina Laboratory Services, |
RCV001143060 | SCV001303558 | uncertain significance | Ovarian hyperstimulation syndrome | 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. |
| OMIM | RCV000017631 | SCV000037908 | pathogenic | Ovarian dysgenesis 1 | 1998-10-01 | no assertion criteria provided | literature only |