ClinVar Miner

Submissions for variant NM_000091.5(COL4A3):c.2954G>T (p.Gly985Val)

gnomAD frequency: 0.00002  dbSNP: rs121912827
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000485138 SCV000568798 uncertain significance not provided 2023-04-19 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Affects a glycine residue in a Gly-X-Y motif in the triple helical region of the COL4A3 gene; This variant is associated with the following publications: (PMID: 11961012, 33838161)
Counsyl RCV000675182 SCV000800814 likely pathogenic Autosomal recessive Alport syndrome 2018-05-23 criteria provided, single submitter clinical testing
Invitae RCV000485138 SCV004294024 likely pathogenic not provided 2023-09-21 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with valine, which is neutral and non-polar, at codon 985 of the COL4A3 protein (p.Gly985Val). This variant is present in population databases (rs121912827, gnomAD 0.01%). This missense change has been observed in individuals with Clinical features of Alport syndrome (PMID: 11961012, 25307543). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 17490). 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 expected to disrupt COL4A3 protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
OMIM RCV000019042 SCV000039329 pathogenic Benign familial hematuria 2002-05-01 no assertion criteria provided literature only
Natera, Inc. RCV001831587 SCV002076412 uncertain significance Alport syndrome 2021-04-07 no assertion criteria provided clinical testing

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