Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Prevention |
RCV004533453 | SCV004115732 | likely pathogenic | FGFR1-related disorder | 2023-09-13 | criteria provided, single submitter | clinical testing | The FGFR1 c.625C>T variant is predicted to result in the amino acid substitution p.Arg209Cys. This variant has been previously reported in individuals with Kallmann syndrome with or without cleft lip/palate (Supplementary table 2, Dodé et al 2009. PubMed ID: 18985070; reported as NM 001174066: c.358C>T, p.R120C in case 3, Xu et al. 2015. PubMed ID: 26199944). This variant was also reported as inherited from an unaffected father in an individual with hypogonadotropic hypogonadism (Akkuş et al. 2016. PubMed ID: 28008864). In addition, the c.625C>T (p.Arg209Cys) variant was identified in an individual with idiopathic hypogonadotropic hypogonadism, his affected uncle and unaffected father (Wang et al 2020. PubMed ID: 32666525). In vitro functional studies using a reporter gene assay found a modest decrease in expression compared to wild type isoform (Wang et al 2020. PubMed ID: 32666525), leading the authors to hypothesize the presence of other unidentified gene variant(s) associated with IHH (Wang et al 2020. PubMed ID: 32666525). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare; and, in Clinvar it is interpreted as likely pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/548670/). In summary, this variant is interpreted as likely pathogenic. |
Yale Center for Mendelian Genomics, |
RCV000662313 | SCV000784645 | likely pathogenic | Hypogonadotropic hypogonadism 2 with or without anosmia | 2016-12-16 | no assertion criteria provided | literature only | |
Department of Urology, |
RCV000662313 | SCV001426681 | likely pathogenic | Hypogonadotropic hypogonadism 2 with or without anosmia | no assertion criteria provided | research |