ClinVar Miner

Submissions for variant NM_001844.5(COL2A1):c.4148C>T (p.Thr1383Met)

gnomAD frequency: 0.00005  dbSNP: rs138498898
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000523016 SCV000617519 uncertain significance not provided 2019-08-20 criteria provided, single submitter clinical testing Identified in a patient with hip pain and avascular necrosis of the femoral head whose niece had a history of epiphyseal dysplasia but did not harbor any variants in the COL2A1 gene (Kannu et al., 2011); also identified in a patient with early-onset bilateral sensorineural hearing loss (Miyagawa et al., 2013); Identified independently and in conjunction with additional variants in individuals referred for connective tissue disorder genetic testing at GeneDx; segregation data is limited or absent at this time; In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Not located in the triple helical region, where the majority of pathogenic missense variants occur (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 23967202, 21671384, 27183340, 30328481)
Genomic Research Center, Shahid Beheshti University of Medical Sciences RCV000022484 SCV000746882 likely pathogenic Avascular necrosis of femoral head, primary, 1 2017-12-18 criteria provided, single submitter clinical testing
Invitae RCV000523016 SCV002313977 likely benign not provided 2023-12-11 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV000523016 SCV003828120 uncertain significance not provided 2022-05-30 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003934848 SCV004755079 uncertain significance COL2A1-related condition 2024-02-13 criteria provided, single submitter clinical testing The COL2A1 c.4148C>T variant is predicted to result in the amino acid substitution p.Thr1383Met. This variant has been reported in the heterozygous state in an individual with avascular necrosis of the femur head (Kannu et al. 2011. PubMed ID: 21671384) and in an individual with deafness (Table S2, Miyagawa et al. 2013. PubMed ID: 23967202). This variant is reported in 0.024% of alleles in individuals of European (Non-Finnish) descent in gnomAD. In ClinVar, this variant has classifications ranging from Likely Benign to Likely Pathogenic (https://www.ncbi.nlm.nih.gov/clinvar/variation/29637/). At this time the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
OMIM RCV000022484 SCV000043773 pathogenic Avascular necrosis of femoral head, primary, 1 2011-07-01 no assertion criteria provided literature only

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