ClinVar Miner

Submissions for variant NM_033380.3(COL4A5):c.4377del (p.Gly1460fs)

dbSNP: rs1603323174
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory of Medical Genetics, National & Kapodistrian University of Athens RCV000789032 SCV000928369 pathogenic X-linked Alport syndrome 2018-05-24 criteria provided, single submitter clinical testing PVS1,PM1,PM2,PP2
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India RCV000789032 SCV003803639 pathogenic X-linked Alport syndrome criteria provided, single submitter clinical testing
King Laboratory, University of Washington RCV000789032 SCV003844195 pathogenic X-linked Alport syndrome 2023-02-28 criteria provided, single submitter research This variant was found in hemizygosity in a male patient with Alport syndrome, in a study of pediatric hearing loss conducted by the King Laboratory (Carlson RJ et al. JAMA-OtoHNS 2023). This patient has a maternal uncle with Alport syndrome, and his mother and grandmother also have renal abnormalities. The patient’s family has no other history of hearing loss. This variant is a single base pair deletion that causes a frameshift leading to the addition of 93 incorrect amino acids and an early stop at position 1547 of the 1691 amino acid COL4A5 protein. As of January 2023, this variant has been reported to ClinVar as pathogenic and is not found on gnomAD. Based on the prediction that this variant leads to a truncated protein, x-linked recessive inheritance pattern in the family, and goodness of fit of genotype to phenotype, we conclude that this variant is pathogenic.
Invitae RCV003660835 SCV004376170 pathogenic not provided 2023-03-01 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 637042). This sequence change creates a premature translational stop signal (p.Gly1454Glufs*94) in the COL4A5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL4A5 are known to be pathogenic (PMID: 9195222, 10752524, 14514738, 24854265, 26809805). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with COL4A5-related conditions (PMID: 34008892).

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