Submissions for variant NM_000283.4(PDE6B):c.313G>A (p.Glu105Lys)

gnomAD frequency: 0.00002  dbSNP: rs398123299

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078554	SCV000110410	uncertain significance	not provided	2013-09-19	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000778735	SCV000915093	uncertain significance	Retinitis pigmentosa	2017-10-05	criteria provided, single submitter	clinical testing	The PDE6B c.313G>A (p.Glu105Lys) missense variant has been reported in two individuals with retinitis pigmentosa, one with the variant in a compound heterozygous state with a missense variant, and the second with an additional missense variant, but the zygosity is not clear (Xu et al. 2014; Costa et al. 2017). The p.Glu105Lys variant was absent from 192 control alleles and is reported at a frequency of 0.00062 in the East Asian population of the Genome Aggregation Database, but this is based on one allele in a region of good sequence coverage, so it is presumed to be rare. Based on the limited clinical evidence, the p.Glu105Lys variant is classified as a variant of unknown significance but suspicious for pathogenicity for autosomal recessive retinitis pigmentosa. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Blueprint Genetics	RCV001074335	SCV001239910	likely pathogenic	Retinal dystrophy	2019-07-10	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001151258	SCV001312372	uncertain significance	Congenital stationary night blindness autosomal dominant 2	2017-10-03	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). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000078554	SCV001516454	uncertain significance	not provided	2024-11-05	criteria provided, single submitter	clinical testing	This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 105 of the PDE6B protein (p.Glu105Lys). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individuals with autosomal recessive retinitis pigmentosa (PMID: 24938718, 28912962, 30718709, 30998820, 33576794). ClinVar contains an entry for this variant (Variation ID: 92767). Invitae Evidence 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 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.
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000778735	SCV000926875	uncertain significance	Retinitis pigmentosa	2018-04-01	no assertion criteria provided	research