Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000780611 | SCV000918027 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2018-09-24 | criteria provided, single submitter | clinical testing | Variant summary: PMM2 c.109C>T (p.Gln37X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g., p.Arg194X). The variant allele was found at a frequency of 0.00014 in 244386 control chromosomes. This frequency is not higher than expected for a pathogenic variant in PMM2 causing Congenital Disorder of Glycosylation Type 1a (0.00014 vs 0.0056), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.109C>T in individuals affected with Congenital Disorder of Glycosylation Type 1a and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV000780611 | SCV000963575 | pathogenic | PMM2-congenital disorder of glycosylation | 2024-01-02 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Gln37*) in the PMM2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in PMM2 are known to be pathogenic (PMID: 19862844). This variant is present in population databases (rs764353860, gnomAD 0.08%). This variant has not been reported in the literature in individuals affected with PMM2-related conditions. ClinVar contains an entry for this variant (Variation ID: 632947). For these reasons, this variant has been classified as Pathogenic. |
| Gene |
RCV001547621 | SCV001767372 | pathogenic | not provided | 2023-08-11 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 19862844) |
| Fulgent Genetics, |
RCV000780611 | SCV002792422 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2022-03-20 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002535677 | SCV003541278 | pathogenic | Inborn genetic diseases | 2022-07-28 | criteria provided, single submitter | clinical testing | The c.109C>T (p.Q37*) alteration, located in exon 2 (coding exon 2) of the PMM2 gene, consists of a C to T substitution at nucleotide position 109. This changes the amino acid from a glutamine (Q) to a stop codon at amino acid position 37. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on the available evidence, this alteration is classified as pathogenic. |
| Baylor Genetics | RCV000780611 | SCV004204840 | likely pathogenic | PMM2-congenital disorder of glycosylation | 2023-10-15 | criteria provided, single submitter | clinical testing |