Total submissions: 6
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Baylor Genetics | RCV001337031 | SCV001530589 | likely pathogenic | Klippel-Feil syndrome 1, autosomal dominant | 2018-11-11 | criteria provided, single submitter | clinical testing | This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported as disease-causing [PMID:23307924] |
Gene |
RCV001753472 | SCV001985468 | uncertain significance | not provided | 2019-06-24 | criteria provided, single submitter | clinical testing | In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function; Published functional studies demonstrate a damaging effect. D57H shown to significantly reduce transcription activation in exogenous reporter assay in COS7 cells (Asai-Coakwell et al., 2013).; This variant is associated with the following publications: (PMID: 23307924, 31589614) |
Labcorp Genetics |
RCV001853075 | SCV002295520 | uncertain significance | Klippel-Feil syndrome 1, autosomal dominant; Isolated microphthalmia 4; Microphthalmia, isolated, with coloboma 6; Leber congenital amaurosis 17 | 2023-11-25 | criteria provided, single submitter | clinical testing | This sequence change replaces aspartic acid, which is acidic and polar, with histidine, which is basic and polar, at codon 57 of the GDF6 protein (p.Asp57His). This variant is present in population databases (rs397514725, gnomAD 0.01%), including at least one homozygous and/or hemizygous individual. This missense change has been observed in individual(s) with clinical features of Leber congenital amaurosis (PMID: 23307924). ClinVar contains an entry for this variant (Variation ID: 60534). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Experimental studies have shown that this missense change affects GDF6 function (PMID: 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. |
Baylor Genetics | RCV000054426 | SCV003841222 | uncertain significance | Leber congenital amaurosis 17 | criteria provided, single submitter | clinical testing | ||
OMIM | RCV000054426 | SCV000082903 | pathogenic | Leber congenital amaurosis 17 | 2013-04-01 | no assertion criteria provided | literature only | |
Prevention |
RCV004757958 | SCV005347906 | uncertain significance | GDF6-related disorder | 2024-04-03 | no assertion criteria provided | clinical testing | The GDF6 c.169G>C variant is predicted to result in the amino acid substitution p.Asp57His. This variant was reported along with a second potentially causative variant in an individual with Leber congenital amaurosis (Asai-Coakwell et al. 2013. PubMed ID: 23307924). This variant is reported in 0.016% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |