ClinVar Miner

Submissions for variant NM_133642.5(LARGE1):c.391G>A (p.Val131Ile)

gnomAD frequency: 0.00027  dbSNP: rs56239539
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000724331 SCV000230241 uncertain significance not provided 2016-01-15 criteria provided, single submitter clinical testing
Athena Diagnostics RCV000178221 SCV000613997 uncertain significance not specified 2017-02-03 criteria provided, single submitter clinical testing
Invitae RCV001087480 SCV000761732 likely benign Muscular dystrophy-dystroglycanopathy type B6 2024-01-29 criteria provided, single submitter clinical testing
GeneDx RCV000724331 SCV000977894 likely benign not provided 2020-01-06 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 28454995)
Mayo Clinic Laboratories, Mayo Clinic RCV000724331 SCV001715619 uncertain significance not provided 2019-04-17 criteria provided, single submitter clinical testing
Ambry Genetics RCV002517723 SCV003749853 likely benign Inborn genetic diseases 2021-06-06 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.
Revvity Omics, Revvity RCV000724331 SCV003816469 uncertain significance not provided 2022-02-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000178221 SCV004122813 uncertain significance not specified 2023-10-12 criteria provided, single submitter clinical testing Variant summary: LARGE1 c.391G>A (p.Val131Ile) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00063 in 254490 control chromosomes in the gnomAD database, including 1 homozygotes. c.391G>A has been reported in the literature in an individual affected with Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A who carried a second variant of uncertain significance in the compound heterozygous state. These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Seven submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Multiple submitters reported the variant with conflicting assessments including four VUS and three likely benign classifications. Based on the evidence outlined above, the variant was classified as uncertain significance.

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