ClinVar Miner

Submissions for variant NM_004370.6(COL12A1):c.4255T>A (p.Tyr1419Asn)

gnomAD frequency: 0.00002  dbSNP: rs758640189
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000553937 SCV000656157 uncertain significance Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 2023-12-09 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 1419 of the COL12A1 protein (p.Tyr1419Asn). This variant is present in population databases (rs758640189, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with COL12A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 475866). 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 COL12A1 protein function with a positive predictive value of 80%. 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.
Revvity Omics, Revvity RCV003144364 SCV003831194 uncertain significance not provided 2021-04-13 criteria provided, single submitter clinical testing
GeneDx RCV003144364 SCV003936344 uncertain significance not provided 2023-06-27 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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