Submissions for variant NM_006269.2(RP1):c.3826C>T (p.Pro1276Ser)

gnomAD frequency: 0.00153  dbSNP: rs151316028

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000178266	SCV000230313	uncertain significance	not provided	2014-12-31	criteria provided, single submitter	clinical testing
Invitae	RCV000178266	SCV001121905	likely benign	not provided	2024-01-09	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001163234	SCV001325253	likely benign	Retinitis pigmentosa	2018-01-13	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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
CeGaT Center for Human Genetics Tuebingen	RCV000178266	SCV004700380	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	RP1: BP4, BS2
PreventionGenetics, part of Exact Sciences	RCV003895200	SCV004711117	likely benign	RP1-related condition	2019-08-06	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001356977	SCV001552286	likely benign	Retinitis pigmentosa 1		no assertion criteria provided	clinical testing	The RP1 p.P1276S variant was identified in a mother and child with familial brain tumors; however, their phenotype was attributed to pathogenic variants in the TP53 and ARTX genes (Nordfors_2018_PMID:29602769). The variant was identified in dbSNP (ID: rs151316028) and ClinVar (classified as likely benign by Illumina and Invitae; and as uncertain significance by EGL Genetic Diagnostics). The variant was identified in control databases in 479 of 282826 chromosomes (2 homozygous) at a frequency of 0.001694, and was observed at the highest allele count in the European (non-Finnish) population in 341 of 129136 chromosomes (freq: 0.002641) (Genome Aggregation Database March 6, 2019, v2.1.1). The p.P1276 residue is not conserved in mammals and computational analyses (MUT Assesor, PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) do not suggest a high likelihood of impact to the protein. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign.
Clinical Genetics, Academic Medical Center	RCV000178266	SCV001920952	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000178266	SCV001971325	likely benign	not provided		no assertion criteria provided	clinical testing