ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.1267C>T (p.Arg423Cys)

gnomAD frequency: 0.00001  dbSNP: rs1270445631
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Genome Diagnostics Laboratory, The Hospital for Sick Children RCV002277973 SCV002565558 uncertain significance Ehlers-Danlos syndrome 2019-12-01 criteria provided, single submitter clinical testing
Invitae RCV003774902 SCV004568521 uncertain significance Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2023-09-23 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with COL1A2-related conditions. 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. 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 expected to disrupt COL1A2 protein function. ClinVar contains an entry for this variant (Variation ID: 1702186). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 423 of the COL1A2 protein (p.Arg423Cys).
Ambry Genetics RCV004047525 SCV005032177 uncertain significance Cardiovascular phenotype 2024-01-29 criteria provided, single submitter clinical testing The p.R423C variant (also known as c.1267C>T), located in coding exon 23 of the COL1A2 gene, results from a C to T substitution at nucleotide position 1267. The arginine at codon 423 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Based on the available evidence, the clinical significance of this alteration remains unclear.

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