Submissions for variant NM_000426.4(LAMA2):c.6832A>G (p.Met2278Val)

gnomAD frequency: 0.00026  dbSNP: rs146854942

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000376263	SCV000460071	uncertain significance	Congenital muscular dystrophy due to partial LAMA2 deficiency	2018-01-12	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
GeneDx	RCV000726647	SCV000572877	uncertain significance	not provided	2017-08-29	criteria provided, single submitter	clinical testing	A variant of uncertain significance has been identified in the LAMA2 gene. The M2278V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The M2278V variant is observed in 15/66734 (0.02%) alleles from individuals of European background (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The M2278V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. However, this substitution occurs at a position that is conserved in mammals. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Eurofins Ntd Llc (ga)	RCV000726647	SCV000701944	uncertain significance	not provided	2016-10-07	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000700908	SCV000829685	likely benign	LAMA2-related muscular dystrophy	2024-01-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000726647	SCV001247109	uncertain significance	not provided	2020-01-01	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001266074	SCV001444246	uncertain significance	Inborn genetic diseases	2022-01-28	criteria provided, single submitter	clinical testing	The c.6832A>G (p.M2278V) alteration is located in exon 48 (coding exon 48) of the LAMA2 gene. This alteration results from a A to G substitution at nucleotide position 6832, causing the methionine (M) at amino acid position 2278 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Mayo Clinic Laboratories, Mayo Clinic	RCV000726647	SCV001714798	uncertain significance	not provided	2022-05-05	criteria provided, single submitter	clinical testing	BP4, PM2
Fulgent Genetics, Fulgent Genetics	RCV002487558	SCV002778381	uncertain significance	Merosin deficient congenital muscular dystrophy; Muscular dystrophy, limb-girdle, autosomal recessive 23	2021-08-05	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000726647	SCV003808185	uncertain significance	not provided	2023-01-19	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000726647	SCV004563185	uncertain significance	not provided	2023-10-20	criteria provided, single submitter	clinical testing