ClinVar Miner

Submissions for variant NM_000093.5(COL5A1):c.1888C>T (p.Arg630Trp)

gnomAD frequency: 0.00011  dbSNP: rs577618553
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000198923 SCV000249800 uncertain significance not provided 2023-09-22 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign in association with a COL5A1-related disorder to our knowledge; 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 (Symoens et al., 2012; HGMD); This variant is associated with the following publications: (PMID: 33206719)
Invitae RCV002229042 SCV000631460 likely benign Ehlers-Danlos syndrome, classic type, 1 2024-01-26 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000559592 SCV000897497 uncertain significance Ehlers-Danlos syndrome, classic type 2018-10-31 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002277474 SCV002565680 benign Ehlers-Danlos syndrome 2021-09-07 criteria provided, single submitter clinical testing
Ambry Genetics RCV002408861 SCV002723837 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-10-19 criteria provided, single submitter clinical testing The p.R630W variant (also known as c.1888C>T), located in coding exon 18 of the COL5A1 gene, results from a C to T substitution at nucleotide position 1888. The arginine at codon 630 is replaced by tryptophan, an amino acid with dissimilar properties. This alteration has been reported in a whole exome sequencing cohort of COVID-19 patients (Benetti E et al. PLoS One, 2020 Nov;15:e0242534). This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000198923 SCV004564739 uncertain significance not provided 2023-04-27 criteria provided, single submitter clinical testing The COL5A1 c.1888C>T; p.Arg630Trp variant (rs577618553), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 212944). This variant is found in the non-Finnish European population with an allele frequency of 0.02% (25/128836 alleles) in the Genome Aggregation Database. Computational analyses predict that this variant is deleterious (REVEL: 0.85). Due to limited information, the clinical significance of this variant is uncertain at this time.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004525898 SCV005039330 likely benign not specified 2024-03-13 criteria provided, single submitter clinical testing Variant summary: COL5A1 c.1888C>T (p.Arg630Trp) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.0001 in 251012 control chromosomes. The observed variant frequency is approximately 3.19 fold of the estimated maximal expected allele frequency for a pathogenic variant in COL5A1 causing Ehlers-Danlos Syndrome phenotype (3.1e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.1888C>T in individuals affected with Ehlers-Danlos Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 212944). Based on the evidence outlined above, the variant was classified as likely benign.
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000198923 SCV001929905 uncertain significance not provided no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000198923 SCV001973477 uncertain significance not provided no assertion criteria provided clinical testing
Zotz-Klimas Genetics Lab, MVZ Zotz Klimas RCV002229042 SCV004101128 uncertain significance Ehlers-Danlos syndrome, classic type, 1 2023-11-02 no assertion criteria provided clinical testing

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