ClinVar Miner

Submissions for variant NM_000171.4(GLRA1):c.920A>G (p.Tyr307Cys) (rs121918410)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001376583 SCV000828951 pathogenic Hereditary hyperekplexia 2019-12-16 criteria provided, single submitter clinical testing This sequence change replaces tyrosine with cysteine at codon 307 of the GLRA1 protein (p.Tyr307Cys). The tyrosine residue is highly conserved and there is a large physicochemical difference between tyrosine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to segregate with hyperekplexia in a multigenerational family, and has been identified in other unrelated individuals affected with the same condition (PMID: 7611730, 11389164, Invitae). The variant has been found in all of these affected individuals in the heterozygous state. This finding is consistent with autosomal dominant inheritance. This variant is also known as p.Tyr279Cys in the literature. ClinVar contains an entry for this variant (Variation ID: 16063). This variant has been reported to affect GLRA1 protein function (PMID: 9009272). A different missense substitution at this codon (p.Tyr307Ser, also known as p.Tyr279Ser) has been reported in an individual affected with hyperekplexia (PMID: 16236274). For these reasons, this variant has been classified as Pathogenic.
Genetics and Prenatal Diagnosis Center,The First Affiliated Hospital of Zhengzhou University RCV000017441 SCV001622420 pathogenic Hyperekplexia 1 2021-05-13 criteria provided, single submitter clinical testing
OMIM RCV000017441 SCV000037713 pathogenic Hyperekplexia 1 1995-07-01 no assertion criteria provided literature only
GeneReviews RCV000017441 SCV000054514 pathologic Hyperekplexia 1 2012-10-04 no assertion criteria provided curation Converted during submission to Pathogenic.

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