ClinVar Miner

Submissions for variant NM_001384140.1(PCDH15):c.3441dup (p.Phe1148fs)

dbSNP: rs770832663
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000409226 SCV000485345 likely pathogenic Usher syndrome type 1F 2015-11-24 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000826148 SCV000967679 pathogenic Rare genetic deafness 2018-03-02 criteria provided, single submitter clinical testing The p.Phe1148fs variant in PCDH15 has been reported in one individual with Usher syndrome, who was compound heterozygous with a second likely pathogenic PCDH15 variant (Lenarduzzi 2015). This variant has been identified in 1/111386 European chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinst itute.org/; dbSNP rs770832663) and has been reported in ClinVar (Variation ID: 3 70113). Although this variant has been seen in the general population, its frequ ency is low enough to be consistent with a recessive carrier frequency. This var iant is predicted to cause a frameshift, which alters the protein?s amino acid s equence beginning at position 1148 and leads to a premature termination codon 8 amino acids downstream. Loss of PCDH15 function is an established disease mechan ism for Usher syndrome. In summary, this variant meets criteria to be classified as pathogenic for autosomal recessive Usher syndrome based on its presence in a n affected individual, extremely low frequency in the general population, and it s predicted impact on the protein. ACMG/AMP Criteria applied: PVS1; PM2; PM3; PP 4.
Labcorp Genetics (formerly Invitae), Labcorp RCV002523845 SCV003441617 pathogenic not provided 2022-06-14 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 370113). This variant is also known as c.3229_3230insA. This premature translational stop signal has been observed in individual(s) with Usher syndrome (PMID: 25575603). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs770832663, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Phe1148Ilefs*8) in the PCDH15 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PCDH15 are known to be pathogenic (PMID: 11398101, 11487575, 14570705).
Baylor Genetics RCV003475937 SCV004200860 pathogenic Autosomal recessive nonsyndromic hearing loss 23 2024-01-08 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV005044605 SCV005675224 pathogenic Autosomal recessive nonsyndromic hearing loss 23; Usher syndrome type 1D; Usher syndrome type 1F 2024-04-02 criteria provided, single submitter clinical testing
Natera, Inc. RCV000409226 SCV001459216 pathogenic Usher syndrome type 1F 2020-09-16 no assertion criteria provided clinical testing

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