Submissions for variant NM_001077365.2(POMT1):c.1478dup (p.Tyr493Ter)

dbSNP: rs727502854

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000150017	SCV000196877	pathogenic	not provided	2016-07-01	criteria provided, single submitter	clinical testing	c.1544_1545insA, p.Tyr515Stop in exon 15 of the POMT1 gene (NM_007171.3). The normal sequence with the bases that are inserted in braces is: GATA{A}CGGC. The Y515X pathogenic variant in the POMT1 gene results in the replacement of a Tyrosine codon with a stop codon at amino acid position 515. The presence of a homozygous pathogenic variant in this position is consistent with a diagnosis of muscular dystrophy-dystroglycanopathy (MDDG), a disorder with an autosomal recessive mode of inheritance. The Y515X pathogenic variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The variant is found in POMT1 panel(s).
Invitae	RCV003764901	SCV004569710	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy	2023-03-18	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 162594). This premature translational stop signal has been observed in individual(s) with POMT1-related conditions (PMID: 24901346). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Tyr515*) 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).