ClinVar Miner

Submissions for variant NM_000215.4(JAK3):c.2141C>T (p.Thr714Met)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003324318 SCV004030093 pathogenic Severe combined immunodeficiency disease 2023-07-12 criteria provided, single submitter clinical testing Variant summary: JAK3 c.2141C>T (p.Thr714Met) results in a non-conservative amino acid change located in the Protein kinase domain (IPR000719) of 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 4.4e-05 in 251400 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in JAK3 causing Severe Combined Immunodeficiency (4.4e-05 vs 0.00094), allowing no conclusion about variant significance. c.2141C>T has been reported in the literature in multiple homozygous individuals affected with Severe Combined Immunodeficiency (Nair_2018, Tezcan_2005). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 30293248, 15644840). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005029981 SCV005655169 pathogenic T-B+ severe combined immunodeficiency due to JAK3 deficiency 2024-04-11 criteria provided, single submitter clinical testing

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