ClinVar Miner

Submissions for variant NM_014646.2(LPIN2):c.584C>T (p.Ala195Val) (rs1226336598)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000703303 SCV000832199 uncertain significance Majeed syndrome 2018-05-03 criteria provided, single submitter clinical testing This sequence change replaces alanine with valine at codon 195 of the LPIN2 protein (p.Ala195Val). The alanine residue is weakly conserved and there is a small physicochemical difference between alanine and valine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with LPIN2-related disease. 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 valine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000703303 SCV000898801 uncertain significance Majeed syndrome 2018-06-29 criteria provided, single submitter clinical testing LPIN2 NM_014646.2 exon 4 p.Ala195Val (c.584C>T): This variant has not been reported in the literature but is present in 2/33582 Latino alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/). This variant is present in ClinVar (Variation ID:468459). Evolutionary conservation and computational predictive tools suggest that this variant may not impact the protein. Of note, splice prediction tools suggest that this variant may affect splicing. However, further studies are needed to understand its impact. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.

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