ClinVar Miner

Submissions for variant NM_000091.4(COL4A3):c.1918G>A (p.Gly640Arg) (rs200672668)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410611 SCV000487304 likely pathogenic Alport syndrome, autosomal recessive 2016-11-10 criteria provided, single submitter clinical testing
GeneDx RCV000489873 SCV000577626 likely pathogenic not provided 2015-12-17 criteria provided, single submitter clinical testing The G640R variant in the COL4A3 gene has been reported previously in trans with another COL4A3 variant in two unrelated individuals with Alport syndrome (Heidet et al., 2001; Storey et al., 2013). The G640R variant was not observed at any significant frequency in approximately 6,500 individuals of European and African American ancestry by the NHLBI Exome Sequencing Project. The G640R 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. In silico analysis is inconsistent in its predictions as to whether or not this variant is damaging to the protein structure/function. However, this substitution occurs at a position in the Gly-X-Y repeat within the triple helical region that is conserved across species.Based on review of the data in the context of the 2015 ACMG standards and guidelines for the interpretation of sequence variants (Richards et al., 2015), we now interpret G640R as a likely pathogenic variant; however, the possibility that it may be a rare benign variant cannot be excluded.

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