Submissions for variant NM_032119.4(ADGRV1):c.12704A>G (p.Tyr4235Cys)

gnomAD frequency: 0.00011  dbSNP: rs200644004

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000606387	SCV000713305	uncertain significance	not specified	2017-06-13	criteria provided, single submitter	clinical testing	The p.Tyr4235Cys variant in GRP98 has been reported in individuals with hearing loss (Miyagawa 2013) and has been identified in 0.03% (35/125796) of European ch romosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitu te.org/; dbSNP rs200644004). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Comp utational prediction tools and conservation analyses suggest that this variant m ay impact the protein, though this information is not predictive enough to deter mine pathogenicity. In summary, the clinical significance of the p.Tyr4235Cys va riant is uncertain.
Fulgent Genetics, Fulgent Genetics	RCV000765852	SCV000897248	uncertain significance	Usher syndrome type 2C; Febrile seizures, familial, 4	2018-10-31	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001151949	SCV001313137	uncertain significance	Usher syndrome type 2C	2017-08-10	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001323988	SCV001514927	likely benign	not provided	2024-10-19	criteria provided, single submitter	clinical testing
GeneDx	RCV001323988	SCV002546694	uncertain significance	not provided	2022-07-05	criteria provided, single submitter	clinical testing	Reported in a cohort of patients with hearing loss in published literature (Miyagawa et al., 2013); clinical and molecular information are limited; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 34426522, 23967202)
Institute of Human Genetics, Univ. Regensburg, Univ. Regensburg	RCV004817817	SCV005071593	uncertain significance	Retinal dystrophy	2022-01-01	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV001323988	SCV001922028	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001323988	SCV001964390	uncertain significance	not provided		no assertion criteria provided	clinical testing