ClinVar Miner

Submissions for variant NM_015404.4(WHRN):c.995G>A (p.Arg332Gln) (rs139193948)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000213530 SCV000270111 likely benign not specified 2015-03-25 criteria provided, single submitter clinical testing p.Arg332Gln in exon 4 of DFNB31: This variant is not expected to have clinical s ignificance due to a lack of conservation across species, including mammals. Of note, 7 mammals have a glutamine (Gln) at this position despite moderate nearby amino acid conservation. In addition, computational prediction tools do not sugg est a high likelihood of impact to the protein. This variant has also been ident ified in 0.16% (16/10078) of African chromosomes by the Exome Aggregation Consor tium (ExAC, http://exac.broadinstitute.org; dbSNP rs139193948).
Invitae RCV001230294 SCV001402769 uncertain significance not provided 2020-10-21 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 332 of the WHRN protein (p.Arg332Gln). The arginine residue is moderately conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs139193948, ExAC 0.2%). This variant has been observed in an individual affected with early-onset hearing loss (PMID: 26969326). ClinVar contains an entry for this variant (Variation ID: 227295). 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.

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