Submissions for variant NM_198271.5(LMOD3):c.1099_1100del (p.Asn367fs)

dbSNP: rs727502799

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000522872	SCV000617841	pathogenic	not provided	2022-09-22	criteria provided, single submitter	clinical testing	Has been reported as a recurrent homozygous variant associated with severe nemaline myopathy (Yuen et al., 2014); 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; This variant is associated with the following publications: (PMID: 25250574, 31572445)
Revvity Omics, Revvity	RCV000149598	SCV002017168	pathogenic	Nemaline myopathy 10	2019-09-06	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000149598	SCV002225386	pathogenic	Nemaline myopathy 10	2024-11-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn367Glnfs*11) in the LMOD3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LMOD3 are known to be pathogenic (PMID: 25250574). This variant is present in population databases (rs727502799, gnomAD 0.05%). This premature translational stop signal has been observed in individual(s) with LMOD3-related conditions (PMID: 25250574). ClinVar contains an entry for this variant (Variation ID: 162218). For these reasons, this variant has been classified as Pathogenic.
Kasturba Medical College, Manipal, Kasturba Medical College, Manipal, Manipal Academy of Higher Education, Manipal, India	RCV000149598	SCV003804246	pathogenic	Nemaline myopathy 10	2023-01-23	criteria provided, single submitter	clinical testing
Neuberg Centre For Genomic Medicine, NCGM	RCV000149598	SCV004176643	likely pathogenic	Nemaline myopathy 10	2023-02-14	criteria provided, single submitter	clinical testing	The frameshift variant c.1099_1100del (p.Asn367GlnfsTer11) in the LMOD3 gene has been reported previously in compound heterozygous state in an individual affected with nemaline myopathy (Yuen et al., 2014). This variant is reported with the allele frequency (0.002%) in the gnomAD Exomes and novel in 1000 Genomes. It is submitted to ClinVar as Pathogenic (Multiple submissions). This variant is predicted to cause a loss of normal protein function through protein truncation. Loss of function variants has been previously reported to be disease causing. For these reasons, this variant has been classified as Likely Pathogenic.
OMIM	RCV000149598	SCV000196574	pathogenic	Nemaline myopathy 10	2014-11-03	no assertion criteria provided	literature only