ClinVar Miner

Submissions for variant NM_001001557.4(GDF6):c.878T>C (p.Met293Thr)

gnomAD frequency: 0.00014  dbSNP: rs762304422
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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 RCV001232658 SCV001405224 uncertain significance Klippel-Feil syndrome 1, autosomal dominant; Isolated microphthalmia 4; Microphthalmia, isolated, with coloboma 6; Leber congenital amaurosis 17 2023-01-11 criteria provided, single submitter clinical testing 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. 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. ClinVar contains an entry for this variant (Variation ID: 959329). This variant has not been reported in the literature in individuals affected with GDF6-related conditions. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces methionine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 293 of the GDF6 protein (p.Met293Thr).
GeneDx RCV003229029 SCV003925922 uncertain significance not provided 2023-05-01 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant has a deleterious effect on protein structure/function
PreventionGenetics, part of Exact Sciences RCV003953595 SCV004774125 uncertain significance GDF6-related disorder 2024-02-08 no assertion criteria provided clinical testing The GDF6 c.878T>C variant is predicted to result in the amino acid substitution p.Met293Thr. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.047% of alleles in individuals of African descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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