ClinVar Miner

Submissions for variant NM_000093.5(COL5A1):c.4652C>T (p.Thr1551Ile)

gnomAD frequency: 0.00002  dbSNP: rs863223460
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000197090 SCV000249842 uncertain significance not provided 2023-03-30 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign in association with a COL5A1-related disorder to our knowledge; 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 (Symoens et al., 2012; HGMD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 29924831)
Illumina Laboratory Services, Illumina RCV000353197 SCV000478582 uncertain significance Ehlers-Danlos syndrome type 7A 2016-06-14 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV002229455 SCV000827136 likely benign Ehlers-Danlos syndrome, classic type, 1 2024-11-19 criteria provided, single submitter clinical testing
Ambry Genetics RCV002336523 SCV002636821 uncertain significance Familial thoracic aortic aneurysm and aortic dissection 2022-03-18 criteria provided, single submitter clinical testing The p.T1551I variant (also known as c.4652C>T), located in coding exon 61 of the COL5A1 gene, results from a C to T substitution at nucleotide position 4652. The threonine at codon 1551 is replaced by isoleucine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
PreventionGenetics, part of Exact Sciences RCV004748648 SCV005342500 uncertain significance COL5A1-related disorder 2024-06-14 no assertion criteria provided clinical testing The COL5A1 c.4652C>T variant is predicted to result in the amino acid substitution p.Thr1551Ile. This variant has been reported in an individual with keratoconus (Table S3, Lucas et al. 2018. PubMed ID: 29924831). This variant is reported in 0.0023% of alleles in individuals of European (Non-Finnish) 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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