Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Broad Center for Mendelian Genomics, |
RCV001004887 | SCV001164376 | uncertain significance | Van Maldergem syndrome 2 | 2018-12-03 | criteria provided, single submitter | research | The heterozygous p.Ser3103Gly variant in FAT4 was identified by our study in the compound heterozygous state, with another VUS, in one individual with Van Maldergem syndrome. The p.Ser3103Gly variant in FAT4 has not been previously reported in individuals with Van Maldergem syndrome and has been identified in 0.003249% (1/30778) of South Asian chromosomes, 0.002980% (1/33556) of Latino chromosomes, and 0.002708% (3/110802) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs764097811). Although this variant has been seen in the general population, its frequency is low enough to be consistent with a recessive carrier frequency. Computational prediction tools and conservation analyses suggest that this variant may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Ser3103Gly variant is uncertain. ACMG/AMP Criteria applied: PM2, BP4 (Richards 2015). |
| Invitae | RCV001860568 | SCV002294089 | uncertain significance | not provided | 2022-07-23 | criteria provided, single submitter | clinical testing | This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 3103 of the FAT4 protein (p.Ser3103Gly). This variant is present in population databases (rs764097811, gnomAD 0.003%). This missense change has been observed in individual(s) with clinical features of FAT4-related conditions (PMID: 28878612). This variant is also known as c.9313A>G (p.Ser3105Gly). ClinVar contains an entry for this variant (Variation ID: 813917). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt FAT4 protein function. 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. |
| Yale Center for Mendelian Genomics, |
RCV001849468 | SCV002106496 | likely pathogenic | Congenital anomaly of kidney and urinary tract | 2018-08-24 | no assertion criteria provided | literature only |