ClinVar Miner

Submissions for variant NM_001195263.2(PDZD7):c.680G>A (p.Arg227His)

dbSNP: rs200730376
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV001089564 SCV001244774 uncertain significance Hearing loss, autosomal recessive 57 2018-04-27 criteria provided, single submitter clinical testing A homozygous missense variant, NM_001195263.1(PDZD7):c.680G>A, has been identified in exon 5 of 17 of the PDZD7 gene. The variant is predicted to result in a minor amino acid change from arginine to histidine at position 227 of the protein (NP_001182192.1(PDZD7):p.(Arg227His)). The arginine residue at this position has very high conservation (100 vertebrates, UCSC), and is located within the PDZ functional domain. In-silico predictions for this variant are consistently pathogenic (Polyphen, SIFT, CADD, Mutation Taster). The variant is absent in population databases (gnomAD, dbSNP, 1000G). This variant has not been previously reported in clinical cases. Based on the information available at the time of curation, this variant has been classified as VARIANT of UNKNOWN SIGNIFICANCE (VUS) with HIGH clinical significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001862658 SCV002137544 uncertain significance not provided 2022-07-12 criteria provided, single submitter clinical testing This missense change has been observed in individual(s) with deafness (PMID: 31827275). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 227 of the PDZD7 protein (p.Arg227His). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 869470). 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: "Not Available"; Align-GVGD: "Class C25"). 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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