Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000696045 | SCV000824590 | likely pathogenic | Glycogen storage disease, type VII | 2023-11-04 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 13 of the PFKM gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in PFKM are known to be pathogenic (PMID: 7825568, 8037209). This variant is present in population databases (rs746348793, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with PFKM-related conditions. ClinVar contains an entry for this variant (Variation ID: 574183). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000696045 | SCV002598606 | likely pathogenic | Glycogen storage disease, type VII | 2022-09-18 | criteria provided, single submitter | clinical testing | Variant summary: PFKM c.1191+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. 4/4 computational tools predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 8e-06 in 251028 control chromosomes (gnomAD). To our knowledge, no occurrence of c.1191+1G>A in individuals affected with Glycogen Storage Disease, Type VII and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters have assessed the variant since 2014: both classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Baylor Genetics | RCV000696045 | SCV004203941 | likely pathogenic | Glycogen storage disease, type VII | 2023-05-25 | criteria provided, single submitter | clinical testing | |
| Natera, |
RCV000696045 | SCV002091080 | likely pathogenic | Glycogen storage disease, type VII | 2021-02-18 | no assertion criteria provided | clinical testing |