Submissions for variant NM_006059.4(LAMC3):c.2066C>T (p.Pro689Leu)

gnomAD frequency: 0.00123  dbSNP: rs113443891

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724723	SCV000225637	uncertain significance	not provided	2015-04-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000724723	SCV000490598	likely benign	not provided	2018-12-13	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 30924900)
Genetic Services Laboratory, University of Chicago	RCV000174351	SCV000595537	uncertain significance	not specified	2017-02-13	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000764801	SCV000895946	uncertain significance	Occipital pachygyria and polymicrogyria	2018-10-31	criteria provided, single submitter	clinical testing
Invitae	RCV000724723	SCV001059302	likely benign	not provided	2024-01-27	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000174351	SCV002600495	uncertain significance	not specified	2022-10-13	criteria provided, single submitter	clinical testing	Variant summary: LAMC3 c.2066C>T (p.Pro689Leu) results in a non-conservative amino acid change located in the Laminin-type EGF domain (IPR002049) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00062 in 282742 control chromosomes, including 1 homozygote (gnomAD). To our knowledge, no occurrence of c.2066C>T in individuals affected with Occipital Pachygyria And Polymicrogyria and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters have assessed the variant since 2014: three classified the variant as uncertain significance and two as likely benign. Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics	RCV002516626	SCV003676766	likely benign	Inborn genetic diseases	2021-09-01	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.
CeGaT Center for Human Genetics Tuebingen	RCV000724723	SCV004699806	likely benign	not provided	2024-01-01	criteria provided, single submitter	clinical testing	LAMC3: BP4
PreventionGenetics, part of Exact Sciences	RCV003927593	SCV004745239	likely benign	LAMC3-related condition	2022-11-10	criteria provided, single submitter	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).