Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001305381 | SCV001494714 | uncertain significance | Klippel-Feil syndrome 1, autosomal dominant; Isolated microphthalmia 4; Microphthalmia, isolated, with coloboma 6; Leber congenital amaurosis 17 | 2023-12-17 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 126 of the GDF6 protein (p.Thr126Met). This variant is present in population databases (rs536331514, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with GDF6-related conditions. ClinVar contains an entry for this variant (Variation ID: 1008100). 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 GDF6 protein function with a negative predictive value of 80%. 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. |
| Ambry Genetics | RCV004036349 | SCV004875910 | uncertain significance | Inborn genetic diseases | 2023-12-17 | criteria provided, single submitter | clinical testing | The c.377C>T (p.T126M) alteration is located in exon 1 (coding exon 1) of the GDF6 gene. This alteration results from a C to T substitution at nucleotide position 377, causing the threonine (T) at amino acid position 126 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |