Submissions for variant NM_001077365.2(POMT1):c.197C>T (p.Pro66Leu)

gnomAD frequency: 0.00006  dbSNP: rs757903559

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000591710	SCV000708845	uncertain significance	not provided	2017-05-24	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000819538	SCV000960203	uncertain significance	Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 66 of the POMT1 protein (p.Pro66Leu). This variant is present in population databases (rs757903559, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of muscular dystrophy-dystroglycanopathy (PMID: 30060766). ClinVar contains an entry for this variant (Variation ID: 502200). 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 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.
GeneDx	RCV000591710	SCV001816842	uncertain significance	not provided	2021-09-27	criteria provided, single submitter	clinical testing	Reported previously with a pathogenic variant in a patient with limb-girdle muscle weakness in published literature, but it is not known whether the variants occurred on the same (in cis) or on different (in trans) chromosomes (Johnson et al., 2018); Reported previously in a patient with suspected muscle disease; however, no further clinical or segregation information was provided (Tpf et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; This variant is associated with the following publications: (PMID: 22549409, 30564623, 32528171, 30060766)
Ambry Genetics	RCV002532650	SCV003593375	uncertain significance	Inborn genetic diseases	2022-07-18	criteria provided, single submitter	clinical testing	The c.197C>T (p.P66L) alteration is located in exon 3 (coding exon 2) of the POMT1 gene. This alteration results from a C to T substitution at nucleotide position 197, causing the proline (P) at amino acid position 66 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Revvity Omics, Revvity	RCV000591710	SCV003811808	uncertain significance	not provided	2019-04-15	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV003459474	SCV004206059	likely pathogenic	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1	2024-03-30	criteria provided, single submitter	clinical testing
Muscle and Diseases Team, Institut de Génétique et Biologie Moléculaire et Cellulaire	RCV004586824	SCV005038608	likely pathogenic	POMT1-related congenital myopathy	2024-03-01	criteria provided, single submitter	research	PM1+PM2+PP1+PP3+PP5