ClinVar Miner

Submissions for variant NM_001077365.2(POMT1):c.174CTT[2] (p.Phe60del) (rs750195040)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000498358 SCV000589544 pathogenic not provided 2017-06-15 criteria provided, single submitter clinical testing The c.180_182delCTT variant in the POMT1 gene has been reported in the compound heterozygous state, opposite of a second POMT1 variant, in a fetus with cobblestone lissencephaly, and in an unrelated child with a congenital α-dystroglycanopathy (Devisme et al., 2012; Yang et al., 2016). Another fetus with cobblestone lissencephaly and the single c.180_182delCTT variant in the POMT1 gene has also been reported (Bouchet et al., 2007). The c.180_182delCTT variant causes an in-frame deletion of one amino acid, Phenylalanine 60, denoted p.Phe60del. This amino acid deletion occurs at a position that is conserved across species. The c.180_182delCTT 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). We interpret c.180_182delCTT as a pathogenic variant.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000850367 SCV000992550 uncertain significance Limb-girdle muscular dystrophy-dystroglycanopathy, type C1 2019-03-20 criteria provided, single submitter research ACMG codes:PM2; PM4
Invitae RCV001205238 SCV001376479 likely pathogenic Limb-girdle muscular dystrophy-dystroglycanopathy, type C1; Congenital muscular dystrophy-dystroglycanopathy with mental retardation, type B1; Walker-Warburg congenital muscular dystrophy 2019-10-09 criteria provided, single submitter clinical testing This variant, c.180_182del, results in the deletion of 1 amino acid(s) of the POMT1 protein (p.Phe60del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs750195040, ExAC 0.009%). This variant has been observed in combination with another POMT1 variant in individuals with cobblestone lissencephaly and/or severe congenital muscular dystrophy (PMID: 22323514, 27193224). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant has also been observed in the heterozygous state in one individual with type II lissencephaly and a second variant was not detected (PMID: 17559086). ClinVar contains an entry for this variant (Variation ID: 431953). 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.

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