ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.2728G>T (p.Ala910Ser) (rs139175351)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000665239 SCV000789328 uncertain significance Usher syndrome type 1F 2017-01-31 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000825424 SCV000966722 uncertain significance not specified 2018-12-27 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Ala910Ser var iant in PCDH15 has been reported in three individuals from Saudi Arabia with hea ring loss (Dallol 2016), and it has also been reported in ClinVar (Variation ID: 550483). This variant has also been identified in 0.12% (29/24020) African chro mosomes by gnomAD ( Computational prediction t ools and conservation analysis do not provide strong support for or against an i mpact to the protein. In summary, while the clinical significance of the p.Ala91 0Ser variant is uncertain, its frequency suggests that it is more likely to be b enign. ACMG/AMP Criteria applied: BS1_Supporting.
Invitae RCV001071361 SCV001236659 uncertain significance not provided 2019-12-27 criteria provided, single submitter clinical testing This sequence change replaces alanine with serine at codon 910 of the PCDH15 protein (p.Ala910Ser). The alanine residue is highly conserved and there is a moderate physicochemical difference between alanine and serine. This variant is present in population databases (rs139175351, ExAC 0.1%). This variant has been observed in individual(s) with hearing impairment (PMID: 27766948). ClinVar contains an entry for this variant (Variation ID: 550483). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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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