ClinVar Miner

Submissions for variant NM_000088.4(COL1A1):c.4067G>A (p.Arg1356His)

gnomAD frequency: 0.00004  dbSNP: rs149820303
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001220548 SCV001392544 uncertain significance Osteogenesis imperfecta type I 2023-02-16 criteria provided, single submitter clinical testing 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) has been performed at Invitae for this missense variant, however the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on COL1A1 protein function. ClinVar contains an entry for this variant (Variation ID: 949148). This missense change has been observed in individual(s) with osteogenesis imperfecta (PMID: 16786509). This variant is present in population databases (rs149820303, gnomAD 0.02%). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1356 of the COL1A1 protein (p.Arg1356His). 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.
GeneDx RCV001773496 SCV002002081 uncertain significance not provided 2022-03-18 criteria provided, single submitter clinical testing Reported in a patient with type II/III osteogenesis imperfecta who also harbored an additional variant (Pollitt et al., 2006); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not located in the triple helical region, where the majority of pathogenic missense variants occur (HGMD); This variant is associated with the following publications: (PMID: 16786509)
GenomeConnect, ClinGen RCV001824937 SCV002075221 not provided Infantile cortical hyperostosis; Ehlers-Danlos syndrome, cardiac valvular type; Ehlers-Danlos syndrome, arthrochalasis type; Osteogenesis imperfecta no assertion provided phenotyping only Variant interpreted as Uncertain significance and reported on 07-01-2020 by Lab or GTR ID 26957. GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.

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