Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000152555 | SCV000201770 | uncertain significance | not specified | 2015-07-20 | criteria provided, single submitter | clinical testing | Variant classified as Uncertain Significance - Favor Benign. The p.Arg322Gln var iant in USH1C has been identified by our laboratory in one individual with heari ng loss who had an alternate explanation of the hearing loss identified (LMM unp ublished data). The p.Arg322Gln variant has also been identified in 9/63664 Euro pean chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadins titute.org; dbSNP rs140424216). The arginine (Arg) at position 322 is not conser ved through species, with star-nosed mole having a glutamine (Gln) at this posit ion, raising the possibility that this change may be tolerated. Additional compu tational prediction tools suggest that the p.Arg322Gln variant may not impact th e protein, though this information is not predictive enough to rule out pathogen icity. In summary, while the clinical significance of the p.Arg322Gln variant is uncertain, the lack of evolutionarily conservation suggests that it is more lik ely to be benign. |
Invitae | RCV001238936 | SCV001411773 | uncertain significance | not provided | 2022-11-01 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 322 of the USH1C protein (p.Arg322Gln). This variant is present in population databases (rs140424216, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with USH1C-related conditions. ClinVar contains an entry for this variant (Variation ID: 166389). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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. |
Natera, |
RCV001273251 | SCV001456081 | uncertain significance | Usher syndrome type 1C | 2020-09-16 | no assertion criteria provided | clinical testing |