Submissions for variant NM_001909.5(CTSD):c.410C>T (p.Ser137Leu)

gnomAD frequency: 0.00005  dbSNP: rs777645484

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000632767	SCV000753953	likely benign	Neuronal ceroid lipofuscinosis	2024-01-08	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002315951	SCV000848012	uncertain significance	Inborn genetic diseases	2016-10-27	criteria provided, single submitter	clinical testing	The p.S137L variant (also known as c.410C>T), located in coding exon 4 of the CTSD gene, results from a C to T substitution at nucleotide position 410. The serine at codon 137 is replaced by leucine, an amino acid with dissimilar properties. This variant was not reported in population based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP), and 1000 Genomes Project. In the ESP, this variant was not observed in 6501 samples (13002 alleles) with coverage at this position. This amino acid position is poorly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx	RCV001821790	SCV002064232	uncertain significance	not provided	2022-01-24	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
PreventionGenetics, part of Exact Sciences	RCV003945587	SCV004757419	likely benign	CTSD-related condition	2022-03-16	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).