ClinVar Miner

Submissions for variant NM_015272.5(RPGRIP1L):c.2932G>A (p.Val978Met)

gnomAD frequency: 0.00009  dbSNP: rs367845452
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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 RCV000636960 SCV000758408 uncertain significance Familial aplasia of the vermis; Meckel-Gruber syndrome 2022-08-21 criteria provided, single submitter clinical testing This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 978 of the RPGRIP1L protein (p.Val978Met). This variant is present in population databases (rs367845452, gnomAD 0.01%). 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: 530904). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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 RCV002477401 SCV000895029 uncertain significance Joubert syndrome 7; Meckel syndrome, type 5; COACH syndrome 3 2024-05-24 criteria provided, single submitter clinical testing
Baylor Genetics RCV001330327 SCV001521973 uncertain significance Meckel syndrome, type 5 2019-09-19 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Natera, Inc. RCV001829788 SCV002087515 uncertain significance Familial aplasia of the vermis 2020-03-09 no assertion criteria provided clinical testing
PreventionGenetics, part of Exact Sciences RCV004533331 SCV004116916 uncertain significance RPGRIP1L-related disorder 2024-05-31 no assertion criteria provided clinical testing The RPGRIP1L c.2932G>A variant is predicted to result in the amino acid substitution p.Val978Met. This variant was reported in one individual with inherited retinal degeneration (Supplementary Table 1. Weisschuh et al. 2024. PubMed ID: 37734845). This variant is reported in 0.011% of alleles in individuals of Latino 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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