Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001852660 | SCV002199645 | uncertain significance | not provided | 2021-06-25 | criteria provided, single submitter | clinical testing | This variant has been observed in individual(s) with Kallmann syndrome and hypogonadotrophic hypogonadism (PMID: 21700882, 25077900). This variant is present in population databases (rs201307896, ExAC 0.1%). This sequence change replaces arginine with glutamine at codon 306 of the HS6ST1 protein (p.Arg306Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Experimental studies have shown that this variant affects HS6ST1 protein function (PMID: 21700882). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. This variant is also known as R296Q. |
Mendelics | RCV002247411 | SCV002517193 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing | |
Ce |
RCV001852660 | SCV004011192 | uncertain significance | not provided | 2023-05-01 | criteria provided, single submitter | clinical testing | HS6ST1: PS4:Moderate, PM5:Supporting, PP3 |
Prevention |
RCV003952386 | SCV004772081 | uncertain significance | HS6ST1-related disorder | 2024-01-08 | criteria provided, single submitter | clinical testing | The HS6ST1 c.917G>A variant is predicted to result in the amino acid substitution p.Arg306Gln. This variant has been reported in the heterozygous state in several unrelated individuals with hypogonadotropic hypogonadism (referred to as R296Q in Tornberg et al. 2011. PubMed ID: 21700882; Miraoui et al. 2013. PubMed ID: 23643382, Table S3; Marcos et al. 2014. PubMed ID: 25077900, Supplementary table 2). In vitro functional studies showed that the p.Arg306Gln variant displayed some reduced enzymatic activity (70-80% of WT activity) (referred to as R296Q in Tornberg et al. 2011. PubMed ID: 21700882). However, this variant is reported in 0.12% of alleles in individuals of European (Non-Finnish)descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |
Breakthrough Genomics, |
RCV001852660 | SCV005187904 | uncertain significance | not provided | criteria provided, single submitter | not provided | ||
OMIM | RCV000032893 | SCV000056664 | risk factor | Hypogonadotropic hypogonadism 15 with anosmia | 2011-07-12 | no assertion criteria provided | literature only |