ClinVar Miner

Submissions for variant NM_001127255.2(NLRP7):c.2248C>G (p.Leu750Val)

gnomAD frequency: 0.00009  dbSNP: rs104895512
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000084003 SCV000914854 pathogenic Hydatidiform mole, recurrent, 1 2018-08-29 criteria provided, single submitter clinical testing The NLRP7 c.2248C>G (p.Leu750Val) variant has been reported three studies and is found in a total of 21 probands with recurrent hydatidiform mole including 15 in a homozygous state, six in a compound heterozygous state, and at least five in a heterozygous state (Kou et al. 2008; Deveault et al. 2009; Estrada et al. 2013). One of the homozygous probands had unaffected parents and sister that were heterozygous for the p.Leu750Val variant (Deveault et al. 2009). The p.Leu750Val variant was reported in five of 460 control chromosomes and is reported at a frequency of 0.005023 in the Latino population of the Exome Aggregation Consortium. Based on the collective evidence, the p.Leu750Val is classified as pathogenic for hydatidiform mole. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Labcorp Genetics (formerly Invitae), Labcorp RCV001061628 SCV001226376 pathogenic not provided 2019-03-13 criteria provided, single submitter clinical testing 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, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. This sequence change replaces leucine with valine at codon 750 of the NLRP7 protein (p.Leu750Val). The leucine residue is moderately conserved and there is a small physicochemical difference between leucine and valine. This variant is present in population databases (rs104895512, ExAC 0.5%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has been observed in multiple individuals affected with autosomal recessive familial recurrent hydatidiform mole 1 (PMID: 18039680, 26956250, 19066229, 23354651) and it is found at high frequency in control individuals of Mexican descent (PMID: 23354651). ClinVar contains an entry for this variant (Variation ID: 97750). 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. For these reasons, this variant has been classified as Pathogenic.
GeneDx RCV001061628 SCV003837474 pathogenic not provided 2022-09-01 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 23354651, 26956250, 24105752, 18039680, 19066229, 21659348, 33583041, 34189227, 33751332)
Unité médicale des maladies autoinflammatoires, CHRU Montpellier RCV000084003 SCV000116125 not provided Hydatidiform mole, recurrent, 1 no assertion provided not provided

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.