ClinVar Miner

Submissions for variant NM_153676.4(USH1C):c.965G>A (p.Arg322Gln) (rs140424216)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized 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 2019-07-30 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 322 of the USH1C protein (p.Arg322Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs140424216, ExAC 0.01%). This variant has not been reported in the literature in individuals 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, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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, Inc. RCV001273251 SCV001456081 uncertain significance Usher syndrome, type 1C 2020-09-16 no assertion criteria provided clinical testing

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