ClinVar Miner

Submissions for variant NM_004629.2(FANCG):c.1367A>T (p.His456Leu)

gnomAD frequency: 0.00013  dbSNP: rs148808709
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000703296 SCV000832192 uncertain significance Fanconi anemia 2022-07-24 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 456 of the FANCG protein (p.His456Leu). This variant is present in population databases (rs148808709, gnomAD 0.02%). This variant has not been reported in the literature in individuals affected with FANCG-related conditions. ClinVar contains an entry for this variant (Variation ID: 579904). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001271255 SCV002584624 uncertain significance Fanconi anemia complementation group G 2022-09-08 criteria provided, single submitter clinical testing The FANCG c.1367A>T (p.His456Leu) missense change has a maximum subpopulation frequency of 0.019% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL predicts a benign effect on protein function, but to our knowledge this prediction has not been confirmed by functional studies. To our knowledge, this variant has not been reported in individuals with Fanconi anemia. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.
Fulgent Genetics, Fulgent Genetics RCV001271255 SCV002814923 uncertain significance Fanconi anemia complementation group G 2021-07-25 criteria provided, single submitter clinical testing
Natera, Inc. RCV001271255 SCV001452299 uncertain significance Fanconi anemia complementation group G 2020-09-16 no assertion criteria provided clinical testing
GenomeConnect - Invitae Patient Insights Network RCV001271255 SCV004228546 not provided Fanconi anemia complementation group G no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 04-08-2019 by Lab Invitae. GenomeConnect-Invitae Patient Insights Network assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. Registry team members make no attempt to reinterpret the clinical significance of the variant. Phenotypic details are available under supporting information.

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