ClinVar Miner

Submissions for variant NM_033380.3(COL4A5):c.5048G>A (p.Arg1683Gln) (rs104886308)

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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics Inc RCV000518046 SCV000612999 likely pathogenic not provided 2018-12-11 criteria provided, single submitter clinical testing Found in at least one symptomatic patient. Predicted to have a damaging effect on the protein. One other pathogenic or likely pathogenic variant affects the same amino acid. Damaging to protein function(s) relevant to disease mechanism.
Gharavi Laboratory,Columbia University RCV000518046 SCV000809274 pathogenic not provided 2018-09-16 criteria provided, single submitter research
Invitae RCV000518046 SCV000961772 pathogenic not provided 2020-10-18 criteria provided, single submitter clinical testing This sequence change replaces arginine with glutamine at codon 1677 of the COL4A5 protein (p.Arg1677Gln). The arginine residue is highly conserved and there is a small physicochemical difference between arginine and glutamine. This variant is present in population databases (rs104886308, ExAC 0.004%). This variant has been observed in several individuals with adult-onset Alport syndrome and has been observed to segregate with adult-onset Alport syndrome in a family (PMID: 9150741, 19919694, 20378821). ClinVar contains an entry for this variant (Variation ID: 10467). Experimental studies have shown that this missense change results in reduced collagen alpha 5(IV) secretion in a mouse model system (PMID: 18083113). For these reasons, this variant has been classified as Pathogenic.
Institute of Human Genetics, University of Leipzig Medical Center RCV000011213 SCV001439915 pathogenic Alport syndrome 1, X-linked recessive 2019-01-01 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000011213 SCV001752777 pathogenic Alport syndrome 1, X-linked recessive 2021-06-30 criteria provided, single submitter clinical testing
GeneDx RCV000518046 SCV001796427 pathogenic not provided 2021-04-08 criteria provided, single submitter clinical testing Published functional studies demonstrate R1683Q results in a loss of formation of the type IV collagen heterotrimers (Kobayashi et al., 2008); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; This variant is associated with the following publications: (PMID: 19919694, 20378821, 9150741, 29144512, 29204651, 29526710, 18083113)
OMIM RCV000011213 SCV000031440 pathogenic Alport syndrome 1, X-linked recessive 2003-06-01 no assertion criteria provided literature only
Research and Development, ARUP Laboratories RCV000011213 SCV000042333 moderate Alport syndrome 1, X-linked recessive 2012-12-04 no assertion criteria provided clinical testing Converted during submission to Pathogenic.
GeneReviews RCV000011213 SCV000057826 pathologic Alport syndrome 1, X-linked recessive 2013-02-28 no assertion criteria provided curation Converted during submission to Pathogenic.
Bioscientia Institut fuer Medizinische Diagnostik GmbH,Sonic Healthcare RCV000011213 SCV000925849 pathogenic Alport syndrome 1, X-linked recessive 2019-02-13 no assertion criteria provided clinical testing
Sydney Genome Diagnostics,Children's Hospital Westmead RCV001328066 SCV001449288 pathogenic Hematuria 2018-05-30 no assertion criteria provided clinical testing This patient is heterozygous for a known pathogenic variant, c.5030G>A (p.Arg1677Gln), in the COL4A5 gene. This variant (dbSNP: rs104886308), located in the C terminal domain of COL4A5, has been previously reported in numerous patients with adult-onset X-linked Alport syndrome in the literature (Barker et al 1997 Hum Genet 99:681-684; Pont-Kingdon et al 2009 BMC Nephrol 10:38; Bekheirnia et al 2010 J Am Soc Nephrol 21:876-883).

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