Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002526128 | SCV000640166 | uncertain significance | Carney-Stratakis syndrome; Pheochromocytoma; Paragangliomas with sensorineural hearing loss; Cowden syndrome 3 | 2020-08-22 | criteria provided, single submitter | clinical testing | 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 missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This variant has not been reported in the literature in individuals with SDHD-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with arginine at codon 16 of the SDHD protein (p.Gly16Arg). The glycine residue is weakly conserved and there is a moderate physicochemical difference between glycine and arginine. |
Prevention |
RCV004722893 | SCV005338588 | uncertain significance | SDHD-related disorder | 2024-07-23 | no assertion criteria provided | clinical testing | The SDHD c.46G>C variant is predicted to result in the amino acid substitution p.Gly16Arg. To our knowledge, this variant has not been reported in the literature or in gnomAD, indicating this variant is rare. This variant is classified as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/465241/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |