Submissions for variant NM_001077365.2(POMT1):c.579_580del (p.Val195fs)

gnomAD frequency: 0.00006  dbSNP: rs1032439203

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV001008771	SCV001168560	pathogenic	not provided	2024-06-17	criteria provided, single submitter	clinical testing	Frameshift 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; Not observed at significant frequency in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge
Baylor Genetics	RCV001328596	SCV001519748	likely pathogenic	Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1	2019-03-01	criteria provided, single submitter	clinical testing	This variant was determined to be likely pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
Revvity Omics, Revvity	RCV001008771	SCV002024724	likely pathogenic	not provided	2023-06-14	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001862754	SCV002139146	pathogenic	Autosomal recessive limb-girdle muscular dystrophy type 2K; Muscular dystrophy-dystroglycanopathy (congenital with intellectual disability), type B1; Walker-Warburg congenital muscular dystrophy	2024-01-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val195Argfs*42) 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 not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with POMT1-related conditions. ClinVar contains an entry for this variant (Variation ID: 817606). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003461312	SCV004206048	likely pathogenic	Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A1	2023-11-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004702574	SCV005204894	pathogenic	Autosomal recessive limb-girdle muscular dystrophy	2024-06-10	criteria provided, single submitter	clinical testing	Variant summary: POMT1 c.579_580delAG (p.Val195ArgfsX42) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. The variant allele was found at a frequency of 8e-06 in 251496 control chromosomes. To our knowledge, no occurrence of c.579_580delAG in individuals affected with Limb-Girdle Muscular Dystrophy, Autosomal Recessive and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 817606). Based on the evidence outlined above, the variant was classified as pathogenic.