ClinVar Miner

Submissions for variant NM_001105206.3(LAMA4):c.3175G>A (p.Val1059Met)

gnomAD frequency: 0.00016  dbSNP: rs373650093
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000171974 SCV000055151 uncertain significance not provided 2013-06-24 criteria provided, single submitter research
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000037361 SCV000061018 uncertain significance not specified 2013-06-07 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The Val1052Met vari ant in LAMA4 has been identified by our laboratory in 1 Sri Lankan individual wi th HCM (LMM unpublished data) and in 1/8600 European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/EVS). Valine (Val) at position 1052 is not conserved in mammals or evolutionarily distant species and one mammal (armadillo) carries a methionine (Met; this variant), suggesting that this change may be tolerated. Additional computational analyses (biochemica l amino acid properties, AlignGVGD, PolyPhen2) also suggest that this variant ma y not impact the protein, though this information is not predictive enough to ru le out pathogenicity. Although collectively this information supports that the V al1052Met variant is more likely benign, additional studies are needed to fully assess its clinical significance.
GeneDx RCV000037361 SCV000250559 benign not specified 2016-04-07 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.
Ambry Genetics RCV000618915 SCV000736740 likely benign Cardiovascular phenotype 2017-01-05 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: 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 RCV000769196 SCV000900572 benign Cardiomyopathy 2018-07-30 criteria provided, single submitter clinical testing
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego RCV001781353 SCV000995756 likely benign Premature ventricular contraction 2018-11-22 criteria provided, single submitter clinical testing
Invitae RCV001088319 SCV001006951 benign Dilated cardiomyopathy 1JJ 2024-01-08 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000037361 SCV004038036 likely benign not specified 2023-08-19 criteria provided, single submitter clinical testing

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