ClinVar Miner

Submissions for variant NM_033380.3(COL4A5):c.4003C>T (p.Pro1335Ser)

gnomAD frequency: 0.00004  dbSNP: rs757653472
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001510276 SCV001717277 benign not provided 2024-03-13 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV002469400 SCV002766059 uncertain significance not specified 2024-03-14 criteria provided, single submitter clinical testing Variant summary: COL4A5 c.3985C>T (p.Pro1329Ser) results in a non-conservative amino acid change in the encoded protein sequence. Four of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.8e-05 in 182928 control chromosomes in the gnomAD database, including 1 homozygotes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3985C>T has been reported in the literature in individuals affected with hearing loss (Miyagawa_2013) and sporadic congenital cataracts (Fan_2020, Li_2023, Liu_2023). These report(s) do not provide unequivocal conclusions about association of the variant with Alport Syndrome 1, X-Linked Recessive. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 32883240, 36729443, 37337769, 23967202). ClinVar contains an entry for this variant (Variation ID: 1164399). Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
GeneDx RCV001510276 SCV005201628 uncertain significance not provided 2023-12-14 criteria provided, single submitter clinical testing Identified in a patient with hearing loss in published literature, however, clinical details were not provided (PMID: 23967202); Identified as hemizygous in patients with congenital cataract in published literature (PMID: 32883240, 36729443); Occurs in the triple helical domain at the Y position in the canonical Gly-X-Y repeat; although this variant may have an effect on normal protein folding and function, missense substitution at the Y position is not a common mechanism of disease; This variant is associated with the following publications: (PMID: 23967202, 32883240, 36729443)

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