Submissions for variant NM_001077365.2(POMT1):c.803G>A (p.Arg268His)

gnomAD frequency: 0.00009  dbSNP: rs369644530

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000502429	SCV000596532	uncertain significance	not specified	2016-09-02	criteria provided, single submitter	clinical testing
Invitae	RCV000543364	SCV000649910	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy	2022-11-01	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 290 of the POMT1 protein (p.Arg290His). This variant is present in population databases (rs369644530, gnomAD 0.008%). This missense change has been observed in individual(s) with clinical features of POMT1-related conditions (Invitae). ClinVar contains an entry for this variant (Variation ID: 436376). 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 not expected to disrupt POMT1 protein function. 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.
Eurofins Ntd Llc (ga)	RCV000728229	SCV000855775	uncertain significance	not provided	2017-07-17	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001166677	SCV001329075	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2K	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000728229	SCV001873863	uncertain significance	not provided	2021-08-31	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 22549409)
Revvity Omics, Revvity	RCV000728229	SCV003811837	uncertain significance	not provided	2023-09-27	criteria provided, single submitter	clinical testing
Department of Genetics, Rouen University Hospital, Normandy Center for Genomic and Personalized Medicine	RCV001264687	SCV001442934	uncertain significance	Neurodevelopmental abnormality	2020-04-03	no assertion criteria provided	clinical testing