ClinVar Miner

Submissions for variant NM_015404.4(WHRN):c.1678G>A (p.Ala560Thr) (rs182072601)

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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 RCV000150389 SCV000197550 likely benign not specified 2014-05-13 criteria provided, single submitter clinical testing Ala560Thr variant in exon 8 of DFNB31: This variant is not expected to have clin ical significance due to a lack of conservation across species, with threonine ( Thr) present at this position in many species including primates and other mamma ls. It has been identified in 0.02% (2/8598) of European American chromosomes b y the NHLBI Exome Sequencing Project and in 1/186 Finnish chromosomes by the 100 0 Genome Project (; dbSNPrs182072601).
Invitae RCV001204350 SCV001375552 uncertain significance not provided 2020-10-05 criteria provided, single submitter clinical testing This sequence change replaces alanine with threonine at codon 560 of the WHRN protein (p.Ala560Thr). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and threonine. This variant is present in population databases (rs182072601, ExAC 0.09%). This variant has not been reported in the literature in individuals with WHRN-related conditions. ClinVar contains an entry for this variant (Variation ID: 163047). 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 threonine 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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