ClinVar Miner

Submissions for variant NM_001375808.2(LPIN2):c.1492T>C (p.Phe498Leu)

gnomAD frequency: 0.00001  dbSNP: rs876660986
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000218346 SCV000279007 uncertain significance not provided 2014-06-02 criteria provided, single submitter clinical testing The F498L variant has not been published as a mutation, nor has it been reported as a benign polymorphism to our knowledge. The F498L variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The F498L variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is highly conserved across vertebrates. 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001854732 SCV002132633 uncertain significance Majeed syndrome 2021-08-27 criteria provided, single submitter clinical testing This sequence change replaces phenylalanine with leucine at codon 498 of the LPIN2 protein (p.Phe498Leu). The phenylalanine residue is moderately conserved and there is a small physicochemical difference between phenylalanine and leucine. This variant is not present in population databases (ExAC no frequency). 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: 234336). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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.

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