Total submissions: 5
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Clin |
RCV003448305 | SCV004175930 | benign | FOXG1 disorder | 2023-10-13 | reviewed by expert panel | curation | The p.Pro84His variant in FOXG1 is present in 1 individual in gnomAD (0.0039%) (not sufficient to meet BS1 criteria). The p.Pro84His variant is observed in at least 20 unaffected individuals (internal database - GeneDx; internal database - Invitae) (BS2). The p.Pro84His variant is found in at least 4 patients with an alternate molecular basis of disease (internal database - Invitae; internal database - GeneDx) (BP5_strong). Computational analysis prediction tools suggest that the p.Pro84His variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Pro84His variant in FOXG1 is classified as Benign based on the ACMG/AMP criteria (BS2, BP5_strong, BP4). |
Gene |
RCV000585314 | SCV000518070 | likely benign | not provided | 2018-07-30 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000585314 | SCV000692784 | uncertain significance | not provided | 2017-10-01 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001365335 | SCV001561601 | benign | Rett syndrome, congenital variant | 2023-11-15 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV004689733 | SCV005185185 | likely benign | not specified | 2024-05-21 | criteria provided, single submitter | clinical testing | Variant summary: FOXG1 c.251C>A (p.Pro84His) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 1066578 control chromosomes. The observed variant frequency is approximately 15.94 fold of the estimated maximal expected allele frequency for a pathogenic variant in FOXG1 causing Rett Syndrome, Congenital Variant phenotype (1e-06). To our knowledge, no occurrence of c.251C>A in individuals affected with Rett Syndrome, Congenital Variant and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 380242). Based on the evidence outlined above, the variant was classified as likely benign. |