ClinVar Miner

Submissions for variant NM_001001557.4(GDF6):c.554A>C (p.His185Pro)

gnomAD frequency: 0.00001  dbSNP: rs763275206
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001952725 SCV002215277 uncertain significance Klippel-Feil syndrome 1, autosomal dominant; Isolated microphthalmia 4; Microphthalmia, isolated, with coloboma 6; Leber congenital amaurosis 17 2024-12-09 criteria provided, single submitter clinical testing This sequence change replaces histidine, which is basic and polar, with proline, which is neutral and non-polar, at codon 185 of the GDF6 protein (p.His185Pro). This variant is present in population databases (rs763275206, gnomAD 0.02%). 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: 1433785). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) 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 RCV004042109 SCV004875912 uncertain significance Inborn genetic diseases 2024-01-08 criteria provided, single submitter clinical testing The c.554A>C (p.H185P) alteration is located in exon 2 (coding exon 2) of the GDF6 gene. This alteration results from a A to C substitution at nucleotide position 554, causing the histidine (H) at amino acid position 185 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Breakthrough Genomics, Breakthrough Genomics RCV004694003 SCV005196038 uncertain significance not provided criteria provided, single submitter not provided

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