ClinVar Miner

Submissions for variant NM_017739.4(POMGNT1):c.1741_1745del (p.Met581fs)

dbSNP: rs749332339
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000411968 SCV000486077 likely pathogenic Muscle eye brain disease 2016-03-23 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV002523855 SCV003761152 likely pathogenic Muscular dystrophy-dystroglycanopathy 2023-01-24 criteria provided, single submitter curation The p.Met581fs variant in POMGNT1 has not been previously reported in the literature in individuals with POMGNT1-associated muscular dystrophy-dystroglycanopathy, but has been identified in 0.005% (1/18360) of East Asian chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs749332339). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID#: 370697) and has been interpreted as likely pathogenic by Counsyl. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 581 and leads to a premature termination codon 3 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the POMGNT1 gene is an established disease mechanism in autosomal recessive POMGNT1-associated muscular dystrophy-dystroglycanopathy. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for POMGNT1-associated muscular dystrophy-dystroglycanopathy. ACMG/AMP Criteria applied: PVS1, PM2 (Richards 2015).

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