ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.1946G>A (p.Arg649Gln)

gnomAD frequency: 0.00009  dbSNP: rs560144848
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001062314 SCV001227108 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 649 of the RPGRIP1L protein (p.Arg649Gln). This variant is present in population databases (rs560144848, gnomAD 0.05%). This variant has not been reported in the literature in individuals affected with RPGRIP1L-related conditions. ClinVar contains an entry for this variant (Variation ID: 856779). 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) performed at Invitae indicates that this missense variant is not expected to disrupt RPGRIP1L 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.
Fulgent Genetics, Fulgent Genetics RCV002482061 SCV002789819 uncertain significance Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 2022-04-11 criteria provided, single submitter clinical testing
Ambry Genetics RCV002553921 SCV003689009 uncertain significance Inborn genetic diseases 2021-09-27 criteria provided, single submitter clinical testing The c.1946G>A (p.R649Q) alteration is located in exon 15 (coding exon 14) of the RPGRIP1L gene. This alteration results from a G to A substitution at nucleotide position 1946, causing the arginine (R) at amino acid position 649 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001832556 SCV002085710 uncertain significance Familial aplasia of the vermis 2020-12-30 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004528366 SCV004106410 uncertain significance RPGRIP1L-related disorder 2023-12-29 no assertion criteria provided clinical testing The RPGRIP1L c.1946G>A variant is predicted to result in the amino acid substitution p.Arg649Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.044% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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