Submissions for variant NM_006059.4(LAMC3):c.4415G>A (p.Arg1472Gln)

gnomAD frequency: 0.00029  dbSNP: rs137894550

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000658433	SCV000780205	uncertain significance	not provided	2024-08-12	criteria provided, single submitter	clinical testing	Reported with a second LAMC3 variant in a fetus with at least one structural abnormality in published literature; however, no further clinical information was provided (PMID: 30266093); In silico analysis indicates that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 33547396, 30266093)
Baylor Genetics	RCV001331532	SCV001523592	uncertain significance	Occipital pachygyria and polymicrogyria	2019-06-20	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Labcorp Genetics (formerly Invitae), Labcorp	RCV000658433	SCV002208763	uncertain significance	not provided	2022-10-17	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 1472 of the LAMC3 protein (p.Arg1472Gln). This variant is present in population databases (rs137894550, gnomAD 0.2%). This missense change has been observed in individual(s) with fetal abnormalities (PMID: 30266093). ClinVar contains an entry for this variant (Variation ID: 546538). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000658433	SCV001808253	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000658433	SCV001968528	likely benign	not provided		no assertion criteria provided	clinical testing