Submissions for variant NM_000283.4(PDE6B):c.1703C>T (p.Thr568Met)

gnomAD frequency: 0.00002  dbSNP: rs369980987

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV001046319	SCV001210216	uncertain significance	not provided	2022-09-13	criteria provided, single submitter	clinical testing	ClinVar contains an entry for this variant (Variation ID: 843645). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on PDE6B protein function. 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. This variant has not been reported in the literature in individuals affected with PDE6B-related conditions. This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 568 of the PDE6B protein (p.Thr568Met). This variant is present in population databases (rs369980987, gnomAD 0.007%).
Illumina Laboratory Services, Illumina	RCV001155046	SCV001316447	uncertain significance	Retinitis pigmentosa	2018-01-15	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	RCV001155047	SCV001316448	benign	Congenital stationary night blindness autosomal dominant 2	2018-01-15	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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Ambry Genetics	RCV004031433	SCV005003381	uncertain significance	Inborn genetic diseases	2022-12-21	criteria provided, single submitter	clinical testing	The c.1703C>T (p.T568M) alteration is located in exon 13 (coding exon 13) of the PDE6B gene. This alteration results from a C to T substitution at nucleotide position 1703, causing the threonine (T) at amino acid position 568 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.