Submissions for variant NM_001105206.3(LAMA4):c.3834G>A (p.Gly1278=)

gnomAD frequency: 0.00006  dbSNP: rs141988342

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037367	SCV000061024	uncertain significance	not specified	2012-04-03	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The Gly1271Gly vari ant in LAMA4 has been identified in 1/7020 European American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washington .edu/EVS/; dbSNP rs141988342). This variant is located in the last base of the e xon, which is part of the 5? splice region. Computational tools do not predict a severe effect on splicing; however, this information is not predictive enough t o rule out pathogenicity. Additional information is needed to fully assess the c linical significance of this variant.
GeneDx	RCV000037367	SCV000513439	benign	not specified	2015-08-24	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000531872	SCV000654013	uncertain significance	Dilated cardiomyopathy 1JJ	2025-01-02	criteria provided, single submitter	clinical testing	This sequence change affects codon 1271 of the LAMA4 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the LAMA4 protein. This variant also falls at the last nucleotide of exon 28, which is part of the consensus splice site for this exon. This variant is present in population databases (rs141988342, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with LAMA4-related conditions. ClinVar contains an entry for this variant (Variation ID: 44379). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. 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.
Ambry Genetics	RCV000620617	SCV000736429	likely benign	Cardiovascular phenotype	2017-06-19	criteria provided, single submitter	clinical testing	This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001170688	SCV001333282	uncertain significance	Cardiomyopathy	2018-08-10	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003964850	SCV004780246	likely benign	LAMA4-related disorder	2021-12-28	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).