ClinVar Miner

Submissions for variant NM_001077365.2(POMT1):c.986+5G>A (rs370096853)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000492919 SCV000582162 uncertain significance not provided 2018-09-25 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the POMT1 gene. The c.1052+5 G>A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.1052+5 G>A variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The c.1052+5 G>A splice site variant is predicted to destroy the canonical splice donor site in intron 10. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Additionally, this substitution occurs at a position that is not conserved. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000648161 SCV000769975 uncertain significance Limb-girdle muscular dystrophy-dystroglycanopathy, type C1; Congenital muscular dystrophy-dystroglycanopathy with mental retardation, type B1; Walker-Warburg congenital muscular dystrophy 2019-07-18 criteria provided, single submitter clinical testing This sequence change falls in intron 10 of the POMT1 gene. It does not directly change the encoded amino acid sequence of the POMT1 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is present in population databases (rs370096853, ExAC 0.04%). This variant has not been reported in the literature in individuals with POMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 429561). Nucleotide substitutions within 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 may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. 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.

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