Submissions for variant NM_000426.4(LAMA2):c.7231G>A (p.Val2411Ile)

gnomAD frequency: 0.00002  dbSNP: rs199814707

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV001155018	SCV001316418	uncertain significance	Congenital muscular dystrophy due to partial LAMA2 deficiency	2018-01-13	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.
Invitae	RCV001242334	SCV001415415	uncertain significance	LAMA2-related muscular dystrophy	2022-08-16	criteria provided, single submitter	clinical testing	This sequence change replaces valine, which is neutral and non-polar, with isoleucine, which is neutral and non-polar, at codon 2411 of the LAMA2 protein (p.Val2411Ile). This variant is present in population databases (rs199814707, gnomAD 0.005%). 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: 906088). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt LAMA2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Baylor Genetics	RCV001329267	SCV001520654	uncertain significance	Merosin deficient congenital muscular dystrophy	2020-06-19	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Mayo Clinic Laboratories, Mayo Clinic	RCV001509286	SCV001715906	uncertain significance	not provided	2020-07-20	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001509286	SCV004160304	likely benign	not provided	2022-09-01	criteria provided, single submitter	clinical testing	LAMA2: BP4