ClinVar Miner

Submissions for variant NM_017739.4(POMGNT1):c.1813C>A (p.Arg605Ser)

dbSNP: rs886044567
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001378149 SCV001575650 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3 2021-11-24 criteria provided, single submitter clinical testing This variant has not been reported in the literature in individuals affected with POMGNT1-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with serine, which is neutral and polar, at codon 605 of the POMGNT1 protein (p.Arg605Ser). ClinVar contains an entry for this variant (Variation ID: 1067007). 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. This variant disrupts the p.Arg605 amino acid residue in POMGNT1. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 19299310, 19679478, 23689641, 24731844). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt POMGNT1 protein function.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV004587149 SCV005077032 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy 2024-04-22 criteria provided, single submitter clinical testing Variant summary: POMGNT1 c.1813C>A (p.Arg605Ser) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 248792 control chromosomes. To our knowledge, no occurrence of c.1813C>A in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. Other missense variants that affect this residue (p.Arg605His, p.Arg605Pro) have been determined to be pathogenic, suggesting this is a functionally important amino acid. ClinVar contains an entry for this variant (Variation ID: 1067007). Based on the evidence outlined above, the variant was classified as likely pathogenic.
Fulgent Genetics, Fulgent Genetics RCV005014515 SCV005647646 likely pathogenic Autosomal recessive limb-girdle muscular dystrophy type 2O; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B3; Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A3; Retinitis pigmentosa 76 2024-04-22 criteria provided, single submitter clinical testing

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