ClinVar Miner

Submissions for variant NM_007315.4(STAT1):c.1765G>T (p.Ala589Ser)

gnomAD frequency: 0.00001  dbSNP: rs745491762
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000482030 SCV000574287 uncertain significance not provided 2019-12-05 criteria provided, single submitter clinical testing In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Geisinger Autism and Developmental Medicine Institute, Geisinger Health System RCV000678288 SCV000804345 uncertain significance Immunodeficiency 31B; Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome; Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency 2018-02-20 criteria provided, single submitter provider interpretation This 8 year old male has a history of autism spectrum disorder, myoclonic jerks, coordination disorder, ADHD, disruptive behavior, tachycardia, joint laxity, recurrent rashes, recurrent respiratory illness, and eosinophilic esophagitis. Genetic testing to date, including exome sequencing, has not yielded a diagnosis. The p.Ala589Ser variant in STAT1 is present in the gnomAD African population at a frequency of 0.025%. Computational prediction models are inconsistent. Subsequent clinical testing showed normal neutrophil function studies and quantitative immunoglobulins.
Labcorp Genetics (formerly Invitae), Labcorp RCV000678288 SCV001232985 uncertain significance Immunodeficiency 31B; Autoimmune enteropathy and endocrinopathy - susceptibility to chronic infections syndrome; Mendelian susceptibility to mycobacterial diseases due to partial STAT1 deficiency 2023-05-01 criteria provided, single submitter clinical testing 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. An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant  is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 424473). This variant has not been reported in the literature in individuals affected with STAT1-related conditions. This variant is present in population databases (rs745491762, gnomAD 0.02%). This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 589 of the STAT1 protein (p.Ala589Ser).
Ambry Genetics RCV004668999 SCV005165358 uncertain significance Inborn genetic diseases 2024-04-17 criteria provided, single submitter clinical testing The c.1765G>T (p.A589S) alteration is located in exon 21 (coding exon 19) of the STAT1 gene. This alteration results from a G to T substitution at nucleotide position 1765, causing the alanine (A) at amino acid position 589 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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