ClinVar Miner

Submissions for variant NM_000090.4(COL3A1):c.1864C>T (p.Pro622Ser)

gnomAD frequency: 0.00001  dbSNP: rs772638774
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000586552 SCV000695360 likely benign not provided 2016-01-13 criteria provided, single submitter clinical testing
Ambry Genetics RCV001189446 SCV000738518 likely benign Familial thoracic aortic aneurysm and aortic dissection 2022-08-03 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Color Diagnostics, LLC DBA Color Health RCV001189446 SCV001356740 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2023-01-27 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 622 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 performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 10/282500 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 RCV001295340 SCV001484257 uncertain significance Ehlers-Danlos syndrome, type 4 2024-01-26 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with serine, which is neutral and polar, at codon 622 of the COL3A1 protein (p.Pro622Ser). This variant is present in population databases (rs772638774, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of Ehlers-Danlos syndrome (PMID: 31719132; Invitae). ClinVar contains an entry for this variant (Variation ID: 495542). 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 COL3A1 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.
GeneDx RCV000586552 SCV001982913 uncertain significance not provided 2022-01-17 criteria provided, single submitter clinical testing Identified in two patients with small vessel disease stroke, however, additional clinical and segregation information were not provided (Tan et al., 2019); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Occurs in the triple helical domain at the X 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 X position is not a common mechanism of disease (Stenson et al., 2014); Reported in ClinVar (ClinVar Variant ID# 495542); This variant is associated with the following publications: (PMID: 31719132, 27535533, 24951259)
All of Us Research Program, National Institutes of Health RCV001295340 SCV004833062 uncertain significance Ehlers-Danlos syndrome, type 4 2024-09-26 criteria provided, single submitter clinical testing This missense variant replaces proline with serine at codon 622 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 performed for this variant. This variant has not been reported in individuals affected with cardiovascular disorders in the literature. This variant has been identified in 10/282500 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.
Fulgent Genetics, Fulgent Genetics RCV005027692 SCV005655397 uncertain significance Ehlers-Danlos syndrome, type 4; Polymicrogyria with or without vascular-type Ehlers-Danlos syndrome 2024-05-03 criteria provided, single submitter clinical testing

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