Submissions for variant NM_001077365.2(POMT1):c.868C>T (p.Arg290Trp)

gnomAD frequency: 0.00005  dbSNP: rs886042627

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725271	SCV000335534	uncertain significance	not provided	2015-10-22	criteria provided, single submitter	clinical testing
GeneDx	RCV000725271	SCV000534415	uncertain significance	not provided	2016-12-19	criteria provided, single submitter	clinical testing	The R312W variant in the POMT1 gene has not been published as a pathogenic variant, nor as a benign variant, to our knowledge. The R312W variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R312W variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Therefore, we interpret R312W as a variant of uncertain significance.
Genetic Services Laboratory, University of Chicago	RCV000332052	SCV000596533	uncertain significance	not specified	2015-12-28	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000332052	SCV000712538	uncertain significance	not specified	2017-08-31	criteria provided, single submitter	clinical testing	The p.Arg312Trp variant in POMT1 has not been previously reported in individuals with myopathy but has been identified in 5 /277130 chromosomes by the Genome Ag gregation Database (gnomAD, http://gnomad.broadinstitute.org). Computational pre diction tools and conservation analysis suggest that the p.Arg312Trp variant may impact the protein, though this information is not predictive enough to determi ne pathogenicity. In summary, the clinical significance of the p.Arg312Trp varia nt is uncertain.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000648159	SCV000769973	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy	2022-09-27	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 312 of the POMT1 protein (p.Arg312Trp). This variant is present in population databases (no rsID available, gnomAD 0.01%). 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: 283451). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). 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.
Revvity Omics, Revvity	RCV000725271	SCV004236452	uncertain significance	not provided	2023-02-08	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV004021137	SCV005008718	uncertain significance	Inborn genetic diseases	2023-12-15	criteria provided, single submitter	clinical testing	The c.934C>T (p.R312W) alteration is located in exon 10 (coding exon 9) of the POMT1 gene. This alteration results from a C to T substitution at nucleotide position 934, causing the arginine (R) at amino acid position 312 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.