ClinVar Miner

Submissions for variant NM_000227.5(LAMA3):c.3618C>A (p.Asn1206Lys) (rs1154232)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 5
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
PreventionGenetics,PreventionGenetics RCV000250312 SCV000303062 benign not specified criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000264313 SCV000407995 benign Laryngo-onycho-cutaneous syndrome 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Clinical Services Laboratory,Illumina RCV000328887 SCV000407996 benign Junctional epidermolysis bullosa gravis of Herlitz 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 and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000250312 SCV000539496 benign not specified 2016-03-29 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency
Integrated Genetics/Laboratory Corporation of America RCV000250312 SCV001361865 benign not specified 2019-05-16 criteria provided, single submitter clinical testing Variant summary: LAMA3 c.3618C>A (p.Asn1206Lys) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.19 in 251140 control chromosomes, predominantly at a frequency of 0.24 within the South Asian subpopulation in the gnomAD database, including 894 homozygotes. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 531 fold of the estimated maximal expected allele frequency for a pathogenic variant in LAMA3 causing Junctional Epidermolysis Bullosa phenotype (0.00045), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. c.3618C>A has been reported in the literature in individuals affected with atopic dermatitis and also in the control population (Stemmler_2014). This report does not provide unequivocal conclusions about association of the variant with Junctional Epidermolysis Bullosa . To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two submitters have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.