Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Illumina Laboratory Services, |
RCV000336093 | SCV000369653 | uncertain significance | Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency | 2016-06-14 | criteria provided, single submitter | clinical testing | The c.126+1_126+4delGTAA variant occurs in a canonical splice site (donor) and is therefore predicted to disrupt or distort the normal gene product. A literature search was performed for the gene and cDNA change. No publications were found based on this search. The variant is reported at a frequency of 0.00170 in the European American population of the Exome Sequencing Project. Based on the variant frequency, disease prevalence, disease penetrance, and inheritance mode, this variant could not be ruled out of causing disease. Due to the potential impact of splice donor variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for glycogen storage disease type XI. |
Invitae | RCV000336093 | SCV001216774 | uncertain significance | Glycogen storage disease due to lactate dehydrogenase M-subunit deficiency | 2024-01-29 | criteria provided, single submitter | clinical testing | This sequence change falls in intron 2 of the LDHA gene. It does not directly change the encoded amino acid sequence of the LDHA protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs776715682, gnomAD 0.1%), and has an allele count higher than expected for a pathogenic variant. This variant has not been reported in the literature in individuals affected with LDHA-related conditions. ClinVar contains an entry for this variant (Variation ID: 303910). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. 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. |
Ce |
RCV001090235 | SCV001245641 | uncertain significance | not provided | 2019-07-01 | criteria provided, single submitter | clinical testing |