ClinVar Miner

Submissions for variant NM_000405.5(GM2A):c.164C>T (p.Pro55Leu)

dbSNP: rs730882196
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000235077 SCV003439242 uncertain significance Tay-Sachs disease, variant AB 2024-05-20 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 55 of the GM2A protein (p.Pro55Leu). This variant is present in population databases (rs730882196, gnomAD no frequency). This missense change has been observed in individual(s) with features of GM2-gangliosidosis (PMID: 25558065, 26203402, 28417072, 33456446). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 183275). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. Studies have shown that this missense change alters GM2A gene expression (PMID: 28417072). 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.
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV000235077 SCV004805033 uncertain significance Tay-Sachs disease, variant AB 2024-03-17 criteria provided, single submitter research
Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre RCV000162097 SCV000196382 likely pathogenic Neurodegenerative illness progressing to crippling dystonia and death with relentless cerebral atrophy 2014-12-01 no assertion criteria provided research
OMIM RCV000235077 SCV000292429 pathogenic Tay-Sachs disease, variant AB 2016-10-21 no assertion criteria provided literature only
Biochemical Molecular Genetic Laboratory, King Abdulaziz Medical City RCV000235077 SCV001133056 likely pathogenic Tay-Sachs disease, variant AB 2019-09-26 no assertion criteria provided clinical testing

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