ClinVar Miner

Submissions for variant NM_001001557.4(GDF6):c.595G>A (p.Ala199Thr)

gnomAD frequency: 0.00005  dbSNP: rs387906794
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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 RCV002513180 SCV003440900 uncertain significance Klippel-Feil syndrome 1, autosomal dominant; Isolated microphthalmia 4; Microphthalmia, isolated, with coloboma 6; Leber congenital amaurosis 17 2023-08-11 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 199 of the GDF6 protein (p.Ala199Thr). 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 missense change has been observed in individual(s) with microphthalmia (PMID: 19864492, 23307924). ClinVar contains an entry for this variant (Variation ID: 30159). 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. Experimental studies have shown that this missense change affects GDF6 function (PMID: 19864492, 23307924). 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.
OMIM RCV000023075 SCV000044366 pathogenic Microphthalmia, isolated, with coloboma 6 2013-04-01 no assertion criteria provided literature only
OMIM RCV000054524 SCV000083002 pathogenic Leber congenital amaurosis 17 2013-04-01 no assertion criteria provided literature only

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