Submissions for variant NM_000520.6(HEXA):c.570G>A (p.Leu190=)

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003041243	SCV003442983	pathogenic	Tay-Sachs disease	2022-06-13	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This variant disrupts the c.570G nucleotide in the HEXA gene. Other variant(s) that disrupt this nucleotide have been determined to be pathogenic (PMID: 33240792; Invitae). This suggests that this nucleotide is clinically significant, and that variants that disrupt this position are likely to be disease-causing. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 5, but is expected to preserve the integrity of the reading-frame (PMID: 2139660). This variant has been observed in individual(s) with Tay-Sachs disease (PMID: 2139660). This variant is not present in population databases (gnomAD no frequency). This sequence change affects codon 190 of the HEXA mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the HEXA protein. RNA analysis indicates that this variant induces altered splicing and likely results in a shortened protein product.