Submissions for variant NM_005559.4(LAMA1):c.1792G>C (p.Glu598Gln)

gnomAD frequency: 0.00203  dbSNP: rs116690149

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000957706	SCV001104521	likely benign	not provided	2025-01-23	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001332623	SCV001525002	uncertain significance	Ataxia - intellectual disability - oculomotor apraxia - cerebellar cysts syndrome	2019-07-23	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics	RCV003169475	SCV003867448	likely benign	Inborn genetic diseases	2023-01-10	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.
GeneDx	RCV000957706	SCV004023557	uncertain significance	not provided	2023-02-07	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004800647	SCV005423243	likely benign	not specified	2024-10-15	criteria provided, single submitter	clinical testing	Variant summary: LAMA1 c.1792G>C (p.Glu598Gln) results in a conservative amino acid change located in the Laminin IV domain (IPR000034) 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 0.00039 in 251482 control chromosomes, predominantly at a frequency of 0.0055 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database exceeds the estimated maximal expected allele frequency for a pathogenic variant in LAMA1 causing Ataxia-Intellectual Disability-Oculomotor Apraxia-Cerebellar Cysts Syndrome phenotype. To our knowledge, no occurrence of c.1792G>C in individuals affected with Ataxia-Intellectual Disability-Oculomotor Apraxia-Cerebellar Cysts Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 777268). Based on the evidence outlined above, the variant was classified as likely benign.
PreventionGenetics, part of Exact Sciences	RCV004553426	SCV004727408	likely benign	LAMA1-related disorder	2019-08-28	no assertion criteria provided	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).