Submissions for variant NM_178857.6(RP1L1):c.217C>T (p.Pro73Ser)

gnomAD frequency: 0.00158  dbSNP: rs202082944

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000376225	SCV000471263	benign	Occult macular dystrophy	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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000659100	SCV000577460	uncertain significance	not provided	2018-10-18	criteria provided, single submitter	clinical testing	The P73S variant in the RP1L1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The P73S variant is observed in 178/65484 (0.3%) alleles from individuals of European background, in the ExAC dataset (Lek et al., 2016). The P73S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved in mammals. In silico analysis predicts this variant is probably damaging to the protein structure/function. We interpret P73S as a variant of uncertain significance.
CeGaT Center for Human Genetics Tuebingen	RCV000659100	SCV000780910	likely benign	not provided	2024-07-01	criteria provided, single submitter	clinical testing	RP1L1: BS2
Labcorp Genetics (formerly Invitae), Labcorp	RCV000659100	SCV001054479	benign	not provided	2024-01-15	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003902411	SCV004722976	likely benign	RP1L1-related disorder	2022-03-22	no assertion criteria provided	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).