Submissions for variant NM_178857.6(RP1L1):c.3971A>G (p.Glu1324Gly)

dbSNP: rs4240659

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000315863	SCV000471136	uncertain significance	Occult macular dystrophy	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.
Genome-Nilou Lab	RCV000315863	SCV002033715	benign	Occult macular dystrophy	2021-11-07	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001796009	SCV002033716	benign	Retinitis pigmentosa 88	2021-11-07	criteria provided, single submitter	clinical testing
Mendelics	RCV001528387	SCV002519989	benign	not specified	2022-05-04	criteria provided, single submitter	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001355893	SCV001550908	uncertain significance	not provided		no assertion criteria provided	clinical testing	The RP1L1 p.Glu1324Gly variant was not identified in the literature nor was it identified in the Cosmic database. The variant was identified in dbSNP (ID: rs4240659), Clinvitae, MutDB, ClinVar (reported as a VUS for occult macular dystrophy by Illumina) and LOVD 3.0 (reported as benign). The variant was not identified in the following control databases: the 1000 Genomes Project, the NHLBI GO Exome Sequencing Project, the Exome Aggregation Consortium (August 8th 2016), or the Genome Aggregation Database (Feb 27, 2017). The p.Glu1324 residue is not conserved across mammals and other organisms and three out of four computational analyses (PolyPhen-2, AlignGVGD, MutationTaster) do not suggest a high likelihood of impact to the protein; this information is not predictive enough to rule out pathogenicity. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528387	SCV001740060	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV001528387	SCV001917454	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV001355893	SCV001956094	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001355893	SCV001975753	likely benign	not provided		no assertion criteria provided	clinical testing