Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001851750 | SCV002184398 | uncertain significance | Klippel-Feil syndrome 1, autosomal dominant; Isolated microphthalmia 4; Microphthalmia, isolated, with coloboma 6; Leber congenital amaurosis 17 | 2021-08-18 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine with leucine at codon 253 of the GDF6 protein (p.Gln253Leu). The glutamine residue is moderately conserved and there is a moderate physicochemical difference between glutamine and leucine. While this variant is present in population databases (rs121909355), the frequency information is unreliable, as metrics indicate poor data quality at this position in the ExAC database. This missense change has been observed in individual(s) with microphthalmia (PMID: 19129173). ClinVar contains an entry for this variant (Variation ID: 8375). 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. 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. |
OMIM | RCV000008881 | SCV000029091 | pathogenic | Isolated microphthalmia 4 | 2009-03-15 | no assertion criteria provided | literature only |