Submissions for variant NM_001077365.2(POMT1):c.1545C>G (p.Ser515Arg)

gnomAD frequency: 0.00114  dbSNP: rs150367385

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000194020	SCV000196867	benign	not specified	2017-10-30	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Eurofins Ntd Llc (ga)	RCV000194020	SCV000226493	likely benign	not specified	2015-09-17	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000194020	SCV000248584	likely benign	not specified	2015-09-18	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000175066	SCV000280635	likely benign	not provided	2016-05-06	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
PreventionGenetics, part of Exact Sciences	RCV000194020	SCV000311736	likely benign	not specified		criteria provided, single submitter	clinical testing
Invitae	RCV001086216	SCV000649882	likely benign	Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy	2024-02-01	criteria provided, single submitter	clinical testing
Mendelics	RCV000988264	SCV001137919	benign	Autosomal recessive limb-girdle muscular dystrophy type 2K	2019-05-28	criteria provided, single submitter	clinical testing
Centre for Mendelian Genomics, University Medical Centre Ljubljana	RCV000680152	SCV001368299	benign	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1	2019-03-26	criteria provided, single submitter	clinical testing	This variant was classified as: Benign. The following ACMG criteria were applied in classifying this variant: BS1,BS2.
CeGaT Center for Human Genetics Tuebingen	RCV000175066	SCV001371091	likely benign	not provided	2024-02-01	criteria provided, single submitter	clinical testing	POMT1: BS1
Athena Diagnostics Inc	RCV000194020	SCV001880377	likely benign	not specified	2020-10-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000194020	SCV002103837	benign	not specified	2022-02-25	criteria provided, single submitter	clinical testing	Variant summary: POMT1 c.1611C>G (p.Ser537Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0016 in 155618 control chromosomes in the gnomAD database, including 1 homozygote. The observed variant frequency is approximately 2.3 fold of the estimated maximal expected allele frequency for a pathogenic variant in POMT1 causing Limb-Girdle Muscular Dystrophy, Autosomal Recessive phenotype (0.00072), strongly suggesting that the variant is benign. Although listed in the literature, to our knowledge, no penetrant association of c.1611C>G in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and a predominant consensus as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Baylor Genetics	RCV000680152	SCV000807617	likely benign	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1		no assertion criteria provided	clinical testing