ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.1976C>T (p.Pro659Leu)

gnomAD frequency: 0.00001  dbSNP: rs756822808
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001183753 SCV001349572 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-11-08 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 659 of the COL3A1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with vascular anomalies (PMID: 28655553). This variant has been identified in 3/250432 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV001248344 SCV001421820 uncertain significance Ehlers-Danlos syndrome, type 4 2024-01-25 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 659 of the COL3A1 protein (p.Pro659Leu). This variant is present in population databases (rs756822808, gnomAD 0.003%). This missense change has been observed in individual(s) with a vascular anomaly (PMID: 28655553). ClinVar contains an entry for this variant (Variation ID: 923218). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
GeneDx RCV001751330 SCV001985729 uncertain significance not provided 2023-08-17 criteria provided, single submitter clinical testing Identified in a patient with vascular anomalies in the published literature (Mattassi et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); 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 (HGMD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 28655553)
All of Us Research Program, National Institutes of Health RCV001248344 SCV004833140 uncertain significance Ehlers-Danlos syndrome, type 4 2024-10-01 criteria provided, single submitter clinical testing This missense variant replaces proline with leucine at codon 659 of the COL3A1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in an individual affected with vascular anomalies (PMID: 28655553). This variant has been identified in 3/250432 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

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