ClinVar Miner

Submissions for variant NM_001845.6(COL4A1):c.1091C>T (p.Pro364Leu)

gnomAD frequency: 0.00001  dbSNP: rs755483519
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Athena Diagnostics RCV000991608 SCV001143212 uncertain significance not provided 2018-12-31 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000991608 SCV002119407 uncertain significance not provided 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 364 of the COL4A1 protein (p.Pro364Leu). This variant is present in population databases (rs755483519, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with COL4A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 804572). 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 not expected to disrupt COL4A1 protein function with a negative predictive value of 95%. 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.
Fulgent Genetics, Fulgent Genetics RCV002488084 SCV002781551 uncertain significance Autosomal dominant familial hematuria-retinal arteriolar tortuosity-contractures syndrome; Brain small vessel disease 1 with or without ocular anomalies; Hemorrhage, intracerebral, susceptibility to; Retinal arterial tortuosity; Microangiopathy and leukoencephalopathy, pontine, autosomal dominant 2024-03-08 criteria provided, single submitter clinical testing
Ambry Genetics RCV004030125 SCV004929919 uncertain significance Inborn genetic diseases 2024-01-04 criteria provided, single submitter clinical testing The c.1091C>T (p.P364L) alteration is located in exon 20 (coding exon 20) of the COL4A1 gene. This alteration results from a C to T substitution at nucleotide position 1091, causing the proline (P) at amino acid position 364 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004740530 SCV005348212 uncertain significance COL4A1-related disorder 2024-09-12 no assertion criteria provided clinical testing The COL4A1 c.1091C>T variant is predicted to result in the amino acid substitution p.Pro364Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.017% of alleles in individuals of Latino descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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