ClinVar Miner

Submissions for variant NM_004370.6(COL12A1):c.6448T>C (p.Tyr2150His)

gnomAD frequency: 0.00023  dbSNP: rs200450866
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000532029 SCV000656184 likely benign Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 2025-02-03 criteria provided, single submitter clinical testing
GeneDx RCV001569986 SCV001794170 uncertain significance not provided 2023-11-13 criteria provided, single submitter clinical testing Reported in a patient with limb-girdle muscular dystrophy (LGMD) who also harbored a pathogenic variant in the CAPN3 gene (PMID: 29970176); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 29970176)
CeGaT Center for Human Genetics Tuebingen RCV001569986 SCV001961979 uncertain significance not provided 2025-01-01 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV001569986 SCV003833359 likely benign not provided 2023-10-26 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004526704 SCV005039073 likely benign not specified 2025-01-14 criteria provided, single submitter clinical testing Variant summary: COL12A1 c.6448T>C (p.Tyr2150His) results in a conservative amino acid change located in the Fibronectin type III (IPR003961) of the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00031 in 248840 control chromosomes. The observed variant frequency is approximately 300 fold of the estimated maximal expected allele frequency for a pathogenic variant in COL12A1 causing Bethlem myopathy 2 phenotype (1e-06). To our knowledge, no occurrence of c.6448T>C in individuals affected with Bethlem myopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 475888). Based on the evidence outlined above, the variant was classified as likely benign.

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