Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000299414 | SCV000402846 | likely benign | Hyper-IgE recurrent infection syndrome 1, autosomal dominant | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Labcorp Genetics |
RCV001306031 | SCV001495387 | likely benign | Hyper-IgE recurrent infection syndrome 1, autosomal dominant; STAT3 gain of function | 2023-04-12 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001420949 | SCV001623414 | likely benign | not specified | 2021-05-05 | criteria provided, single submitter | clinical testing | Variant summary: STAT3 c.1519G>T (p.Val507Phe) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 5.2e-05 in 251476 control chromosomes. The observed variant frequency is approximately 24 fold of the estimated maximal expected allele frequency for a pathogenic variant in STAT3 causing Hyper IgE Syndrome phenotype (2.2e-06), strongly suggesting that the variant is benign. c.1519G>T has been reported in the literature (Kang_2018). This report however, does not provide unequivocal conclusions about association of the variant with Hyper IgE Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (n=1) or likely benign (n=1). Based on the evidence outlined above, the variant was classified as likely benign. |