ClinVar Miner

Submissions for variant NM_014646.2(LPIN2):c.2671G>A (p.Asp891Asn) (rs200648652)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000395862 SCV000408467 uncertain significance Majeed syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx RCV000480316 SCV000565115 uncertain significance not provided 2017-06-22 criteria provided, single submitter clinical testing To our knowledge, the D891N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant. The D891N variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry by the NHLBI Exome Sequencing Project. It is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved and 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 variant or a rare benign variant.
Genome Diagnostics Laboratory,University Medical Center Utrecht RCV000395862 SCV000743504 likely benign Majeed syndrome 2014-10-09 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000395862 SCV000744775 likely benign Majeed syndrome 2017-01-04 criteria provided, single submitter clinical testing
Invitae RCV000395862 SCV000766472 uncertain significance Majeed syndrome 2019-12-30 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 891 of the LPIN2 protein (p.Asp891Asn). The aspartic acid residue is weakly conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs200648652, ExAC 0.05%). This variant has not been reported in the literature in individuals with LPIN2-related disease. ClinVar contains an entry for this variant (Variation ID: 326632). 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 asparagine 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. 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.
Blueprint Genetics RCV000480316 SCV000927191 uncertain significance not provided 2017-03-06 criteria provided, single submitter clinical testing
GenomeConnect, ClinGen RCV000395862 SCV000840196 not provided Majeed syndrome no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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