Submissions for variant NM_001077365.2(POMT1):c.727C>T (p.Arg243Ter)

dbSNP: rs398124247

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000081494	SCV000196873	pathogenic	not provided	2023-03-28	criteria provided, single submitter	clinical testing	Observed with a nonsense variant on the opposite allele (in trans) in a fetus with cobblestone lissencephaly, neural tube defect, and kidney and digestive malformations (Devisme et al., 2012); Not observed at significant frequency in large population cohorts (gnomAD); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; This variant is associated with the following publications: (PMID: 27066551, 28182637, 34853893, 22323514, 35606784)
Eurofins Ntd Llc (ga)	RCV000081494	SCV000233114	pathogenic	not provided	2013-08-02	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000081494	SCV002019493	pathogenic	not provided	2022-08-30	criteria provided, single submitter	clinical testing
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000081494	SCV002818235	pathogenic	not provided	2022-12-17	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV002513831	SCV003246064	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy	2023-10-19	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg265*) in the POMT1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in POMT1 are known to be pathogenic (PMID: 12369018, 15637732, 16575835). This variant is present in population databases (rs398124247, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with congenital muscular dystrophy (PMID: 22323514, 27066551). ClinVar contains an entry for this variant (Variation ID: 95468). For these reasons, this variant has been classified as Pathogenic.
Illumina Laboratory Services, Illumina	RCV003314560	SCV004014742	pathogenic	Myopathy caused by variation in POMT1	2023-02-14	criteria provided, single submitter	clinical testing	The POMT1 c.793C>T (p.Arg265Ter) nonsense variant results in the premature termination of the protein at amino acid position 265. Loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay is expected. This variant has been reported in at least three individuals including in two individuals in whom the variant was found in a compound heterozygous state and in one individual in whom the variant was found in a homozygous state (PMID: 22323514; PMID: 27066551; PMID: 35606784). These individuals showed clinical features of congenital muscular dystrophy-dystroglycanopathy, severe bilateral ventriculomegaly, cerebral hypoplasia, respiratory distress, microphthalmia, macrocephaly, holoprosencephaly, and anorectal malformation. This variant is reported in the Genome Aggregation Database in two alleles total at a frequency of 0.000018 in the European Non-Finnish population (version 2.1.1). Based on the available evidence, the c.793C>T (p.Arg265Ter) variant is classified as pathogenic for POMT1-related myopathies.
Baylor Genetics	RCV003474683	SCV004204065	pathogenic	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1	2024-01-15	criteria provided, single submitter	clinical testing