ClinVar Miner

Submissions for variant NM_001079.4(ZAP70):c.988C>T (p.Leu330Phe)

gnomAD frequency: 0.00005  dbSNP: rs371574765
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000815944 SCV000956424 uncertain significance ZAP70-Related Severe Combined Immunodeficiency 2022-09-19 criteria provided, single submitter clinical testing This sequence change replaces leucine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 330 of the ZAP70 protein (p.Leu330Phe). This variant is present in population databases (rs371574765, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with ZAP70-related conditions. ClinVar contains an entry for this variant (Variation ID: 659011). 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: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available"). 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.
Illumina Laboratory Services, Illumina RCV001137247 SCV001297170 uncertain significance Combined immunodeficiency due to ZAP70 deficiency 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.
Fulgent Genetics, Fulgent Genetics RCV002495152 SCV002776982 uncertain significance Combined immunodeficiency due to ZAP70 deficiency; Autoimmune disease, multisystem, infantile-onset, 2 2022-02-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV004028867 SCV004982394 uncertain significance Inborn genetic diseases 2023-03-01 criteria provided, single submitter clinical testing The c.988C>T (p.L330F) alteration is located in exon 9 (coding exon 7) of the ZAP70 gene. This alteration results from a C to T substitution at nucleotide position 988, causing the leucine (L) at amino acid position 330 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Breakthrough Genomics, Breakthrough Genomics RCV004693365 SCV005187824 uncertain significance not provided criteria provided, single submitter 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.