ClinVar Miner

Submissions for variant NM_001077365.2(POMT1):c.697_699del (p.Asn233del)

gnomAD frequency: 0.00001  dbSNP: rs761863400
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000384984 SCV000477652 uncertain significance Limb-Girdle Muscular Dystrophy, Recessive 2016-06-14 criteria provided, single submitter clinical testing
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000850366 SCV000992549 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2K 2019-03-20 criteria provided, single submitter research ACMG codes: PM2; PM3; PM4; PP3; PP5; PM2
Invitae RCV001861343 SCV002161308 uncertain significance Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy 2021-09-01 criteria provided, single submitter clinical testing This variant, c.697_699del, results in the deletion of 1 amino acid(s) of the POMT1 protein (p.Asn233del), but otherwise preserves the integrity of the reading frame. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has not been reported in the literature in individuals affected with POMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 365275). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Victorian Clinical Genetics Services, Murdoch Childrens Research Institute RCV002470848 SCV002768638 uncertain significance Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1 2019-08-28 criteria provided, single submitter clinical testing A heterozygous in-frame deletion variant was identified, NM_007171.3(POMT1):c.697_699del in exon 8 of 20 of the POMT1 gene. The variant is predicted to result in an in-frame deletion of a single amino acid at position 233 of the protein NP_009102.3(POMT1):p.(Asn233del). The asparagine at this position has low conservation (100 vertebrates, UCSC), but is located within the PMT functional domain. The variant is present in the gnomAD population database at a frequency of #% (0.0008% (2 heterozygotes; 0 homozygotes). The variant has been previously reported as a VUS (ClinVar). Based on information available at the time of curation, this variant has been classified as a VARIANT of UNCERTAIN SIGNIFICANCE (VUS) with LOW CLINICAL RELEVANCE.
PreventionGenetics, part of Exact Sciences RCV004530476 SCV004113368 likely pathogenic POMT1-related disorder 2023-02-15 criteria provided, single submitter clinical testing The POMT1 c.697_699delAAT variant is predicted to result in an in-frame deletion (p.Asn233del). The c.697_699delAAT nucleotides also reside at the end of exon 8 in alternative biologically relevant POMT1 transcripts (eg. NM_001077365.2) and deletion of these nucleotides is predicted to result in defective splicing by several in silico programs (Alamut Visual Plus v1.6.1). This variant was reported in the compound heterozygous state in an individual with a POMT1-related disorder (Table S2 - Bowling et al 2022. PubMed ID: 34930662). At PreventionGenetics, we have observed the c.697_699delAAT variant with a loss-of-function variant in POMT1 in a patient with suspected dystroglycanopathy (internal data). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD (http://gnomad.broadinstitute.org/variant/9-134385380-CAAT-C). This variant is interpreted as likely pathogenic.
GeneDx RCV003441850 SCV004170064 uncertain significance not provided 2023-05-12 criteria provided, single submitter clinical testing Observed with a pathogenic variant on the opposite allele (in trans) in a hospitalized infant in published literature, although clinical information was not provided (Bowling et al., 2022); In-frame deletion of 1 amino acid in a non-repeat region; Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports a deleterious effect on protein structure/function; In-silico analysis is inconclusive as to whether the variant alters gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown; This variant is associated with the following publications: (PMID: 34930662)
Athena Diagnostics RCV003441850 SCV004229900 uncertain significance not provided 2022-09-27 criteria provided, single submitter clinical testing Available data are insufficient to determine the clinical significance of the variant at this time. The frequency of this variant in the general population is uninformative in assessment of its pathogenicity (http://gnomad.broadinstitute.org). Computational tools disagree on the variant's effect on normal protein function.
Revvity Omics, Revvity RCV003441850 SCV004236458 uncertain significance not provided 2023-02-27 criteria provided, single submitter clinical testing

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