ClinVar Miner

Submissions for variant NM_001375808.2(LPIN2):c.1781C>T (p.Pro594Leu)

gnomAD frequency: 0.00025  dbSNP: rs139826951
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000219050 SCV000279370 uncertain significance not provided 2018-06-22 criteria provided, single submitter clinical testing The P594L variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The P594L variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). The P594L variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. In summary, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001217505 SCV001389348 uncertain significance Majeed syndrome 2022-08-24 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 594 of the LPIN2 protein (p.Pro594Leu). This variant is present in population databases (rs139826951, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with LPIN2-related conditions. ClinVar contains an entry for this variant (Variation ID: 234498). 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 leucine 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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001217505 SCV001472029 uncertain significance Majeed syndrome 2019-08-01 criteria provided, single submitter clinical testing The LPIN2 c.1781C>T; p.Pro594Leu variant (rs139826951), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 234498). This variant is found in the general population with an overall allele frequency of 0.009 % (24 / 281,290 alleles) in the Genome Aggregation Database. The proline at codon 594 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Pro594Leu variant is uncertain at this time.
Revvity Omics, Revvity RCV001217505 SCV003817038 uncertain significance Majeed syndrome 2022-10-18 criteria provided, single submitter clinical testing

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