ClinVar Miner

Submissions for variant NM_024426.6(WT1):c.314C>G (p.Ala105Gly)

gnomAD frequency: 0.00008  dbSNP: rs948061247
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000545211 SCV000657622 likely benign Drash syndrome; Frasier syndrome; Wilms tumor 1; 11p partial monosomy syndrome 2024-01-19 criteria provided, single submitter clinical testing
Mendelics RCV000709150 SCV000838441 uncertain significance Wilms tumor 1 2018-07-02 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000763735 SCV000894619 uncertain significance Aniridia 1; Drash syndrome; Frasier syndrome; Meacham syndrome; Mesothelioma, malignant; Nephrotic syndrome, type 4; Wilms tumor 1; 11p partial monosomy syndrome 2018-10-31 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV003139859 SCV003823799 uncertain significance not provided 2022-06-05 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV003139859 SCV004129975 uncertain significance not provided 2023-06-01 criteria provided, single submitter clinical testing
Baylor Genetics RCV003459256 SCV004208929 uncertain significance Drash syndrome 2023-09-15 criteria provided, single submitter clinical testing
Human Developmental Genetics, Institut Pasteur RCV001568364 SCV001786680 uncertain significance Disorder of sexual differentiation 2021-08-15 no assertion criteria provided research Paternal inheritance
PreventionGenetics, part of Exact Sciences RCV004740323 SCV005362508 uncertain significance WT1-related disorder 2024-09-23 no assertion criteria provided clinical testing The WT1 c.299C>G variant is predicted to result in the amino acid substitution p.Ala100Gly. This variant (also described as c.314C>G, p.Ala105Gly in NM_024426.6) has been reported in the homozygous state in a pair of siblings with steroid-resistant nephrotic syndrome (SRNS) who were also apparently homozygous for another missense variant (p.Arg586Gly) in the NPHS1 gene (McCarthy et al. 2013. PubMed ID: 23349334). Of note, both of these individuals were reported to have a more severe phenotype than a third sibling who was also homozygous for the NPHS1 variant but negative for WT1 p.Ala100Gly. The p.Ala100Gly variant has also been observed in the heterozygous state in individuals with various WT1-associated phenotypes including breast cancer (Table S3, Guindalini et al. 2022. PubMed ID: 35264596), primary ovarian insufficiency (Table S7, Heddar et al. 2022. PubMed ID: 36099812), and disorders of sex development (DSD) (Zidoune et al. 2022. PubMed ID: 36110220). This variant is reported in 0.058% of alleles in individuals of Latino descent in gnomAD; however, the quality of this data is questionable and should be treated with caution. This variant is interpreted as uncertain by multiple laboratories in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/476699/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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