ClinVar Miner

Submissions for variant NM_000090.3(COL3A1):c.1864C>T (p.Pro622Ser) (rs772638774)

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Total submissions: 4
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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 RCV000622094 SCV000738518 uncertain significance Cardiovascular phenotype 2016-03-21 criteria provided, single submitter clinical testing The p.P622S variant (also known as c.1864C>T), located in coding exon 26 of the COL3A1 gene, results from a C to T substitution at nucleotide position 1864. The proline at codon 622 is replaced by serine, an amino acid with somesimilar properties. Based on data from ExAC, the Tallele has an overall frequency of approximately 0.005% (6/121056). The highest observed frequency was 0.01% (1/10108) of Africanalleles (Exome Aggregation Consortium (ExAC), Cambridge, MA (URL: http://exac.broadinstitute.org) [Accessed March 18, 2016]).This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6503 samples (13006 alleles) with coverage at this position. This amino acid position is well conserved in available vertebrate species; however,serineis the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Color Health, Inc RCV001189446 SCV001356740 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2019-09-26 criteria provided, single submitter clinical testing
Invitae RCV001295340 SCV001484257 uncertain significance Ehlers-Danlos syndrome, type 4 2020-10-29 criteria provided, single submitter clinical testing This sequence change replaces proline with serine at codon 622 of the COL3A1 protein (p.Pro622Ser). The proline residue is highly conserved and there is a moderate physicochemical difference between proline and serine. This variant is present in population databases (rs772638774, ExAC 0.01%). This variant has been observed in individual(s) with lacunar stroke (PMID: 31719132). ClinVar contains an entry for this variant (Variation ID: 495542). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: Deleterious; PolyPhen-2: Not Available; Align-GVGD: Class C. The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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. 5

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