Submissions for variant NM_032119.4(ADGRV1):c.4666G>A (p.Glu1556Lys)

gnomAD frequency: 0.00044  dbSNP: rs200955930

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724689	SCV000227850	uncertain significance	not provided	2015-04-02	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000176233	SCV000711043	uncertain significance	not specified	2017-06-06	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Glu1556Lys va riant in GPR98 has not been previously reported in the literature, but has been reported in ClinVar (Variation ID:195624). This variant has been identified in 0 .09% (110/120782) of European chromosomes by the Genome Aggregation Database (gn omAD, http://gnomad.broadinstitute.org; dbSNP rs200955930). Although this varian t has been seen in the general population, its frequency is not high enough to r ule out a pathogenic role. Computational prediction tools and conservation analy ses suggest that this variant may not impact the protein, though this informatio n is not predictive enough to rule out pathogenicity. The glutamic acid (Glu) at position 1556 is not highly conserved in mammals and evolutionary distant speci es, and 2 mammals (mouse and opossum) carry a lysine (Lys), raising the possibil ity that this change at this position may be tolerated. In summary, while the cl inical significance of the p.Glu1556Lys variant is uncertain, these data suggest that it is more likely to be benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000724689	SCV001210142	benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001151342	SCV001312463	uncertain significance	Usher syndrome type 2C	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000724689	SCV001792415	likely benign	not provided	2021-01-26	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000176233	SCV002500589	uncertain significance	not specified	2022-03-22	criteria provided, single submitter	clinical testing
Athena Diagnostics	RCV000724689	SCV002771274	uncertain significance	not provided	2021-11-02	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000724689	SCV001924994	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000724689	SCV001967174	uncertain significance	not provided		no assertion criteria provided	clinical testing