Submissions for variant NM_206933.4(USH2A):c.4445C>T (p.Thr1482Ile)

gnomAD frequency: 0.00010  dbSNP: rs200790812

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000378867	SCV000354096	uncertain significance	Usher syndrome type 2A	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.
Illumina Laboratory Services, Illumina	RCV000265612	SCV000354097	uncertain significance	Retinitis pigmentosa	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	RCV000840094	SCV000982010	likely benign	not provided	2018-03-28	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000840094	SCV001197638	likely benign	not provided	2024-11-11	criteria provided, single submitter	clinical testing
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center	RCV000840094	SCV002061395	uncertain significance	not provided	2021-06-17	criteria provided, single submitter	clinical testing	BP4, PM3_Supporting
Mayo Clinic Laboratories, Mayo Clinic	RCV000840094	SCV004224787	uncertain significance	not provided	2022-11-04	criteria provided, single submitter	clinical testing	BP4, PM2
Ambry Genetics	RCV004021420	SCV004975818	uncertain significance	Inborn genetic diseases	2024-03-12	criteria provided, single submitter	clinical testing	The c.4445C>T (p.T1482I) alteration is located in exon 21 (coding exon 20) of the USH2A gene. This alteration results from a C to T substitution at nucleotide position 4445, causing the threonine (T) at amino acid position 1482 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc.	RCV000378867	SCV002093900	likely benign	Usher syndrome type 2A	2019-11-11	no assertion criteria provided	clinical testing