ClinVar Miner

Submissions for variant NM_033056.4(PCDH15):c.16del (p.Tyr6fs) (rs397517451)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000824736 SCV000063394 pathogenic Rare genetic deafness 2012-05-07 criteria provided, single submitter clinical testing The Tyr6fs variant (PCDH15) has been reported in the literature (Zheng 2005, Ouy ang 2005). This frameshift variant is predicted to alter the protein?s amino aci d sequence beginning at position 6 and lead to a premature termination codon 6 a mino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. In summary, this variant meets our criteria to be classified as pathogenic.
Counsyl RCV000039705 SCV000799256 likely pathogenic Usher syndrome type 1F 2018-04-09 criteria provided, single submitter clinical testing
GeneDx RCV001008080 SCV001167819 pathogenic not provided 2018-11-27 criteria provided, single submitter clinical testing The c.16delT pathogenic variant in the PCDH15 gene has been reported previously in association with Usher syndrome type I. It was identified as heterozygous in one affected individual who was also heterozygous for a variant in CHD23 (Zheng et al., 2005), and as heterozygous in an unrelated affected individual with no second variant identified (Ouyeng et al. 2005). The deletion causes a frameshift starting with codon Tyrosine 6, changes this amino acid to an Isoleucine residue and creates a premature Stop codon at position 6 of the new reading frame, denoted p.Tyr6IlefsX6. This pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. It is is not observed in large population cohorts (Lek et al., 2016). In summary, we interpret this variant as pathogenic.
OMIM RCV000005223 SCV000025401 pathogenic USHER SYNDROME, TYPE ID/F, DIGENIC 2005-01-01 no assertion criteria provided literature only
GeneReviews RCV000219366 SCV000268761 pathogenic Usher syndrome type 1 2016-05-19 no assertion criteria provided literature only

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