ClinVar Miner

Submissions for variant NM_000089.4(COL1A2):c.1076A>G (p.Asn359Ser)

gnomAD frequency: 0.00001  dbSNP: rs755584404
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000176027 SCV000227611 uncertain significance not provided 2014-10-20 criteria provided, single submitter clinical testing
Invitae RCV001852166 SCV002289386 uncertain significance Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1 2021-09-04 criteria provided, single submitter clinical testing 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. This variant disrupts the p.Asn359 amino acid residue in COL1A2. Other variant(s) that disrupt this residue have been observed in individuals with COL1A2-related conditions (PMID: 29947050), which suggests that this may be a clinically significant amino acid residue. 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 COL1A2 protein function. ClinVar contains an entry for this variant (Variation ID: 195453). This missense change has been observed in individual(s) with osteogenesis imperfecta (PMID: 26402641). This variant is present in population databases (rs755584404, ExAC 0.06%). This sequence change replaces asparagine with serine at codon 359 of the COL1A2 protein (p.Asn359Ser). The asparagine residue is moderately conserved and there is a small physicochemical difference between asparagine and serine.
Ambry Genetics RCV002415756 SCV002720269 uncertain significance Cardiovascular phenotype 2021-04-26 criteria provided, single submitter clinical testing The p.N359S variant (also known as c.1076A>G), located in coding exon 20 of the COL1A2 gene, results from an A to G substitution at nucleotide position 1076. The asparagine at codon 359 is replaced by serine, an amino acid with highly similar properties. This alteration has been reported in a skeletal dysplasia cohort (Bae JS et al. Genet Med, 2016 06;18:563-9). This amino acid position is not well conserved in available vertebrate species, and serine is 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.

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