Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000945934 | SCV001092009 | likely benign | Ullrich congenital muscular dystrophy 2; Bethlem myopathy 2 | 2023-12-21 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001593138 | SCV001823497 | likely benign | not provided | 2020-07-17 | criteria provided, single submitter | clinical testing | |
Revvity Omics, |
RCV001593138 | SCV003833388 | uncertain significance | not provided | 2021-12-10 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV001356650 | SCV001551877 | benign | not specified | no assertion criteria provided | clinical testing | The COL12A1 p.Val1218Met variant was not identified in the literature nor was it identified in ClinVar. The variant was identified in dbSNP (ID: rs201749138), Cosmic (FATHMM prediction: pathogenic; score=0.79) and LOVD 3.0 (classified as likely benign). The variant was identified in control databases in 95 of 280420 chromosomes at a frequency of 0.000339 (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: East Asian in 81 of 19490 chromosomes (freq: 0.004156), Latino in 6 of 35270 chromosomes (freq: 0.00017), European (non-Finnish) in 7 of 128376 chromosomes (freq: 0.000055) and South Asian in 1 of 30590 chromosomes (freq: 0.000033), but not in the African, Ashkenazi Jewish, European (Finnish), and Other populations. The p.Val1218 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and 2 of 4 in silico or computational prediction software programs (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer) predict a greater than 10% difference in splicing; this is not very predictive of pathogenicity. In summary, based on the above information this variant meets our laboratory's criteria to be classified as benign. |