Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
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, |
RCV001274198 | SCV001458042 | uncertain significance | Congenital lactic acidosis, Saguenay-Lac-Saint-Jean type | 2020-01-24 | no assertion criteria provided | clinical testing |