Submissions for variant NM_000426.4(LAMA2):c.1657C>T (p.Arg553Ter)

dbSNP: rs1303773212

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000523102	SCV000621651	likely pathogenic	not provided	2018-06-28	criteria provided, single submitter	clinical testing	The R553X variant in the LAMA2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The R553X variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016). We interpret R553X as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000709844	SCV003019334	pathogenic	LAMA2-related muscular dystrophy	2023-10-04	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg553*) in the LAMA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in LAMA2 are known to be pathogenic (PMID: 18700894, 32904964). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This variant has not been reported in the literature in individuals affected with LAMA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 452811). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics	RCV003470661	SCV004190429	likely pathogenic	Merosin deficient congenital muscular dystrophy	2023-10-03	criteria provided, single submitter	clinical testing
GenomeConnect, ClinGen	RCV000709844	SCV000840175	not provided	LAMA2-related muscular dystrophy		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.