ClinVar Miner

Submissions for variant NM_001845.6(COL4A1):c.4940C>T (p.Pro1647Leu)

gnomAD frequency: 0.00001  dbSNP: rs201767532
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CeGaT Center for Human Genetics Tuebingen RCV000658679 SCV000780464 uncertain significance not provided 2017-11-01 criteria provided, single submitter clinical testing
Invitae RCV000658679 SCV001563811 uncertain significance not provided 2023-04-26 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. ClinVar contains an entry for this variant (Variation ID: 546730). This variant has not been reported in the literature in individuals affected with COL4A1-related conditions. This variant is present in population databases (rs201767532, gnomAD 0.006%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1647 of the COL4A1 protein (p.Pro1647Leu).
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002470944 SCV002768585 uncertain significance COL4A1 or COL4A2-related cerebral small vessel disease 2020-10-15 criteria provided, single submitter clinical testing Based on the classification scheme VCGS_Germline_v0.6.1, this variant is classified as 3B-VUS. Following criteria are met: 0102 - Loss of function is a known mechanism of disease for this gene. 0104 - Mechanism of disease for this gene is dominant negative. 0107 - This gene is known to be associated with autosomal dominant disease. 0200 - Variant is predicted to result in a missense amino acid change from proline to leucine (exon 52). 0302 - Variant is present in gnomAD >=0.0002 and <0.001 for dominant indication (4 heterozygotes, 0 homozygotes). 0309 - An alternative amino acid change at the same position has been observed in gnomAD (1 heterozygote, 0 homozygotes). 0501 - Missense variant consistently predicted to be damaging by in-silico tools or highly conserved with a major amino acid change. 0600 - Variant is located in an annotated domain or motif that does not have a well established function (C4 domain; NCBI). 0705 - No comparable variants in relevant codon/region have previous evidence for pathogenicity. 0804 - This variant has been previously reported as a VUS (ClinVar). 0905 - No published segregation evidence has been identified for this variant. 1007 - No published functional evidence has been identified for this variant. 1207 - Parental origin of the variant is unresolved.
Revvity Omics, Revvity RCV000658679 SCV004235401 uncertain significance not provided 2023-03-28 criteria provided, single submitter clinical testing

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