Submissions for variant NM_018100.4(EFHC1):c.1270G>T (p.Ala424Ser)

dbSNP: rs796052418

Total submissions: 1

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000187365	SCV000240950	uncertain significance	not provided	2013-10-16	criteria provided, single submitter	clinical testing	p.Pro21Ser (CCG>TCG): c.61 C>T in exon 1 of the CLN5 gene (NM_006493.2). The Pro21Ser missense change was previously reported in a patient with a clinical suspicion of juvenile neuronal ceroid lipofuscinosis who did not have a second identifiable mutation in the CLN5 gene (Kousi et al., 2012). It has also been observed previously at GeneDx in several other patients who did not have a second detectable mutation in the CLN5 gene. The amino acid substitution is non-conservative, as a non-polar Proline residue is replaced by a polar Serine reside, and the loss of a bulky Proline may alter the secondary structure of the protein. However, it alters a position in the signal peptide that is not conserved across species or in related proteins, and mutations have not been reported at nearby codons (Kousi et al., 2012). One in silico model suggests Pro21Ser may be damaging to protein structure/function but others predict it is likely not pathogenic. Therefore, based on the currently available information, it is unclear whether Pro21Ser is a disease-causing mutation or a rare benign variant. The variant is found in EPILEPSY panel(s).