Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000498552 | SCV000589593 | pathogenic | not provided | 2022-05-04 | criteria provided, single submitter | clinical testing | Published functional studies demonstrate a damaging effect on binding ability and inositol phosphate production (Meysing et al., 2004); In silico analysis supports that this variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 15240592, 29419413, 31200363, 23643382, 20696889, 22745237, 34198905, 31589614) |
Invitae | RCV000498552 | SCV003525848 | pathogenic | not provided | 2023-05-24 | criteria provided, single submitter | clinical testing | This variant is also known as two separate variants, c.30T>A (p.Asn10Lys) and c.31C>A (p.Gln11Lys). This variant, c.30_31delinsAA, is a complex sequence change that results in the deletion of 2 and insertion of 2 amino acid(s) in the GNRHR protein (p.Asn10_Gln11delinsLysLys). Information on the frequency of this variant in the gnomAD database is not available, as this variant may be reported differently in the database. This variant has been observed in individual(s) with Kallman syndrome or hypogonadotropic hypogonadism (PMID: 15240592, 31200363, 34198905; Invitae). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 189195). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. Experimental studies have shown that this variant affects GNRHR function (PMID: 15240592). For these reasons, this variant has been classified as Pathogenic. |
Athena Diagnostics Inc | RCV000498552 | SCV004229678 | pathogenic | not provided | 2022-11-11 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population is consistent with pathogenicity (http://gnomad.broadinstitute.org). This variant segregates with disease in multiple families. Assessment of experimental evidence suggests this variant results in abnormal protein function. (PMID: 15240592) 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. |
OMIM | RCV000030919 | SCV000037682 | pathogenic | Hypogonadotropic hypogonadism 7 with or without anosmia | 2004-07-01 | no assertion criteria provided | literature only |