ClinVar Miner

Submissions for variant NM_004370.6(COL12A1):c.1175G>A (p.Arg392His)

gnomAD frequency: 0.00004  dbSNP: rs755195861
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000546858 SCV000656125 uncertain significance Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 2023-12-09 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 392 of the COL12A1 protein (p.Arg392His). This variant is present in population databases (rs755195861, gnomAD 0.006%). This missense change has been observed in individual(s) with clinical features of COL12A1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 475842). 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 COL12A1 protein function with a negative 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 RCV003144363 SCV003831195 uncertain significance not provided 2021-04-13 criteria provided, single submitter clinical testing
GeneDx RCV003144363 SCV003936345 uncertain significance not provided 2023-06-27 criteria provided, single submitter clinical testing Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Ambry Genetics RCV003278916 SCV003962940 uncertain significance Inborn genetic diseases 2023-03-20 criteria provided, single submitter clinical testing The c.1175G>A (p.R392H) alteration is located in exon 9 (coding exon 8) of the COL12A1 gene. This alteration results from a G to A substitution at nucleotide position 1175, causing the arginine (R) at amino acid position 392 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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