ClinVar Miner

Submissions for variant NM_001845.6(COL4A1):c.922G>A (p.Gly308Arg) (rs370677625)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000478856 SCV000572806 uncertain significance not provided 2017-02-06 criteria provided, single submitter clinical testing The G308R variant in the COL4A1 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The G308R variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The G308R variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and is located in the triple helical domain. In silico analysis predicts this variant is probably damaging to the protein structure/function. As an alternate mechanism, splice predictor models indicate that this sequence change may create a new cryptic donor site in exon 17, upstream of the natural splicing donor site, which may cause abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, we interpret G308R as a variant of uncertain significance.
GenomeConnect, ClinGen RCV000509469 SCV000607212 not provided COL4A1-Related Disorder no assertion provided phenotyping only GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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