ClinVar Miner

Submissions for variant NM_133259.4(LRPPRC):c.2072C>T (p.Ser691Leu)

gnomAD frequency: 0.00002  dbSNP: rs372341254
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197246 SCV000251686 uncertain significance not provided 2014-10-03 criteria provided, single submitter clinical testing p.Ser691Leu (TCA>TTA): c.2072 C>T in exon 20 of the LRPPRC gene (NM_133259.3). The S691L variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The S691L variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is moderately 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).
Invitae RCV000197246 SCV003297823 uncertain significance not provided 2021-10-27 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with leucine, which is neutral and non-polar, at codon 691 of the LRPPRC protein (p.Ser691Leu). This variant is present in population databases (rs372341254, gnomAD 0.006%). 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: 214621). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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 RCV003343691 SCV004067698 uncertain significance Inborn genetic diseases 2023-06-22 criteria provided, single submitter clinical testing The c.2072C>T (p.S691L) alteration is located in exon 20 (coding exon 20) of the LRPPRC gene. This alteration results from a C to T substitution at nucleotide position 2072, causing the serine (S) at amino acid position 691 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV001274198 SCV001458042 uncertain significance Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type 2020-01-24 no assertion criteria provided clinical testing

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