Submissions for variant NM_001105206.3(LAMA4):c.1959T>C (p.Asp653=)

gnomAD frequency: 0.00074  dbSNP: rs143269044

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000154646	SCV000204321	uncertain significance	not specified	2015-09-28	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Asp646Asp var iant in LAMA4 has been identified by our laboratory in 1 individual with mild re duction of both right and left ventricle function and has been identified in 0.1 4% (94/66734) of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs143269044). This variant is located in the last three bases of the exon, which is part of the 5? splice region. Computa tional tools do not suggest an impact to splicing. However, this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p.Asp646Asp variant is uncertain, these data suggest that it is more likely to be benign.
GeneDx	RCV000154646	SCV000250528	benign	not specified	2015-07-02	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	RCV000460131	SCV000556717	likely benign	Dilated cardiomyopathy 1JJ	2024-01-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000617800	SCV000736479	likely benign	Cardiovascular phenotype	2017-12-11	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	RCV000770215	SCV000901645	benign	Cardiomyopathy	2018-09-10	criteria provided, single submitter	clinical testing
Klaassen Lab, Charite University Medicine Berlin	RCV000853180	SCV000995895	uncertain significance	Arrhythmogenic right ventricular cardiomyopathy	2019-07-03	criteria provided, single submitter	research
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000460131	SCV001474493	likely benign	Dilated cardiomyopathy 1JJ	2019-12-20	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000154646	SCV001925147	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001699045	SCV001926841	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000154646	SCV001955357	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001699045	SCV001971619	likely benign	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003952761	SCV004772471	likely benign	LAMA4-related disorder	2019-07-23	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).