Submissions for variant NM_178857.6(RP1L1):c.292G>A (p.Asp98Asn)

gnomAD frequency: 0.00007  dbSNP: rs372108562

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001164432	SCV001326559	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001365866	SCV001562151	uncertain significance	not provided	2023-12-07	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 98 of the RP1L1 protein (p.Asp98Asn). This variant is present in population databases (rs372108562, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with RP1L1-related conditions. ClinVar contains an entry for this variant (Variation ID: 911778). 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 RP1L1 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.
Ambry Genetics	RCV002558591	SCV003684685	uncertain significance	Inborn genetic diseases	2024-07-17	criteria provided, single submitter	clinical testing	The c.292G>A (p.D98N) alteration is located in exon 2 (coding exon 1) of the RP1L1 gene. This alteration results from a G to A substitution at nucleotide position 292, causing the aspartic acid (D) at amino acid position 98 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences	RCV003396779	SCV004120584	uncertain significance	RP1L1-related disorder	2023-03-09	criteria provided, single submitter	clinical testing	The RP1L1 c.292G>A variant is predicted to result in the amino acid substitution p.Asp98Asn. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0086% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/8-10480420-C-T). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.