Submissions for variant NM_000171.4(GLRA1):c.1108G>A (p.Gly370Ser)

gnomAD frequency: 0.00939  dbSNP: rs116474260

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000031885	SCV000455424	likely benign	Hyperekplexia 1	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000454994	SCV000539244	likely benign	not specified	2016-03-28	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: DM? in HGMD, frequency
Labcorp Genetics (formerly Invitae), Labcorp	RCV001507199	SCV000638477	benign	Hereditary hyperekplexia	2024-02-01	criteria provided, single submitter	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000031885	SCV000743539	benign	Hyperekplexia 1	2014-10-09	criteria provided, single submitter	clinical testing
Mendelics	RCV000031885	SCV001137013	likely benign	Hyperekplexia 1	2019-05-28	criteria provided, single submitter	clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard	RCV000031885	SCV001435247	likely benign	Hyperekplexia 1		criteria provided, single submitter	research	The heterozygous p.Gly370Ser variant, sometimes called p.Gly342Ser or p.Gly378Ser due to a difference in cDNA numbering, in GLRA1 has been identified in an individual with hyperekplexia and their unaffected parent (PMID: 10817489). This variant has also been identified in >1% of European (non-Finnish) chromosomes and 7 homozygotes by ExAC (http://gnomad.broadinstitute.org/). In vitro functional studies provide some evidence that the p.Gly370Ser variant may not impact protein function (PMID: 10817489). However, these types of assays may not accurately represent biological function. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely benign for hyperekplexia.
GeneDx	RCV001705618	SCV001900661	benign	not provided	2019-10-22	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 27535533, 26764160, 27884173, 10817489, 20981092, 25333069, 20631190)
Molecular Genetics, Royal Melbourne Hospital	RCV000031885	SCV002503663	benign	Hyperekplexia 1	2023-05-04	criteria provided, single submitter	clinical testing	European Non-Finnish population allele frequency is 1.473% (rs116474260, 1959/128696 alleles, 15 homozygotes in gnomAD v2.1). Based on the classification scheme RMH Modified ACMG/AMP Guidelines v1.5.1, this variant is classified as BENIGN. Following criteria are met: BA1
Breakthrough Genomics, Breakthrough Genomics	RCV001705618	SCV005226613	likely benign	not provided		criteria provided, single submitter	not provided
GeneReviews	RCV000031885	SCV000054499	pathologic	Hyperekplexia 1	2012-10-04	flagged submission	curation	Converted during submission to Pathogenic.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000031885	SCV000734388	benign	Hyperekplexia 1		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003924880	SCV004739185	benign	GLRA1-related disorder	2019-03-05	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).