ClinVar Miner

Submissions for variant NM_133259.4(LRPPRC):c.2569A>G (p.Arg857Gly) (rs200138144)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000977664 SCV001125583 likely benign not provided 2020-12-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001139785 SCV001299971 uncertain significance Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000977664 SCV001548890 uncertain significance not provided no assertion criteria provided clinical testing The LRPPRC p.Arg857Gly variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs200138144) and LOVD 3.0 (classified as likely benign). The variant was identified in control databases in 57 of 282320 chromosomes at a frequency of 0.0002019 (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: Ashkenazi Jewish in 33 of 10356 chromosomes (freq: 0.003187), Latino in 14 of 35426 chromosomes (freq: 0.000395), Other in 2 of 7208 chromosomes (freq: 0.000278) and European (non-Finnish) in 8 of 128728 chromosomes (freq: 0.000062), but was not observed in the African, East Asian, European (Finnish), or South Asian populations. The p.Arg857 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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