ClinVar Miner

Submissions for variant NM_004130.3(GYG1):c.143+3G>C (rs370652040)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000387284 SCV000329983 pathogenic not provided 2017-07-14 criteria provided, single submitter clinical testing The c.143+3 G>C splice site variant in the GYG1 gene has been previously reported in association with polyglucoasen body myopathy in several unrelated individuals who were homozygous for c.143+3 G>C or heterozygous for c.143+3 G>C and a second pathogenic variant in the GYG1 gene (Malfatti et al., 2014; Akman et al., 2016). Functional analysis of c.143+3 G>C found that it results in abnormal splicing, leading to skipping of exon 2 (Malfatti et al., 2014). Therefore, we interpret c.143+3 G>C to be a pathogenic variant.
Invitae RCV001054146 SCV001218447 pathogenic Glycogen storage disease XV; Polyglucosan body myopathy 2 2020-01-03 criteria provided, single submitter clinical testing This sequence change falls in intron 2 of the GYG1 gene. It does not directly change the encoded amino acid sequence of the GYG1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs370652040, ExAC 0.03%). This variant has been observed in several individuals and families affected with polyglucosan body myopathy (PMID: 26652229, 25272951, 29264399). ClinVar contains an entry for this variant (Variation ID: 162661). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Experimental studies have shown that this variant disrupts mRNA splicing (PMID:25272951, 29264399). For these reasons, this variant has been classified as Pathogenic.
Undiagnosed Diseases Network,NIH RCV001090151 SCV001245599 pathogenic Glycogen storage disease XV 2019-09-17 criteria provided, single submitter clinical testing
OMIM RCV000150098 SCV000196922 pathogenic Polyglucosan body myopathy 2 2014-12-01 no assertion criteria provided literature only

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