ClinVar Miner

Submissions for variant NM_133259.4(LRPPRC):c.908G>A (p.Arg303His)

gnomAD frequency: 0.00019  dbSNP: rs745653250
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000199259 SCV000251667 uncertain significance not provided 2014-05-19 criteria provided, single submitter clinical testing p.Arg303His (CGT>CAT): c.908 G>A in exon 8 of the LRPPRC gene (NM_133259.3). The R303H variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The R303H variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic mutation or a rare benign variant. The variant is found in MITONUC-MITOP panel(s).
Baylor Genetics RCV001274204 SCV001528480 uncertain significance Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type 2018-10-28 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Fulgent Genetics, Fulgent Genetics RCV001274204 SCV002781916 uncertain significance Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type 2021-07-27 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000199259 SCV005813273 uncertain significance not provided 2024-10-22 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 303 of the LRPPRC protein (p.Arg303His). This variant is present in population databases (rs745653250, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with LRPPRC-related conditions. ClinVar contains an entry for this variant (Variation ID: 214602). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is expected to disrupt LRPPRC protein function with a positive predictive value of 80%. 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.
Natera, Inc. RCV001274204 SCV001458052 uncertain significance Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type 2019-10-28 no assertion criteria provided clinical testing

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