ClinVar Miner

Submissions for variant NM_015404.4(WHRN):c.1696G>C (p.Val566Leu) (rs189654215)

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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 RCV000038880 SCV000062558 likely benign not specified 2011-10-05 criteria provided, single submitter clinical testing Val566Leu in exon 8 of DFNB31: This variant is not expected to have clinical sig nificance because dog, cat, cow, chicken, frog, elephant, and opossum have a leu cine at this position despite high nearby amino acid conservation. The Val566Leu variant occurs in the third to last three base of the exon which is part of the splicing consensus sequence. However, splicing prediction programs suggest no i mpact to splicing.
Invitae RCV001213992 SCV001385655 uncertain significance not provided 2020-06-10 criteria provided, single submitter clinical testing This sequence change replaces valine with leucine at codon 566 of the WHRN protein (p.Val566Leu). The valine residue is weakly conserved and there is a small physicochemical difference between valine and leucine. This variant is present in population databases (rs189654215, ExAC 0.1%). This variant has not been reported in the literature in individuals with WHRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 45662). 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 leucine 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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