Submissions for variant NM_022464.5(SIL1):c.947dup (p.Arg317fs)

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000778754	SCV000915118	pathogenic	Marinesco-Sjögren syndrome	2018-12-12	criteria provided, single submitter	clinical testing	The SIL1 c.947dupT (p.Arg317GlufsTer35) variant results in a frameshift and is predicted to result in premature termination of the protein. The p.Arg317GlufsTer35 has been reported in a total of six individuals with Marinesco-Sjogren syndrome (Senderek et al. 2005; Krieger et al. 2013; Pajusalu et al. 2015). Of these, the variant was found in a homozygous state in two affected cases and in a compound heterozygous state in four affected cases, two of whom were siblings. The p.Arg317GlufsTer35 variant was absent from 160 control subjects and is reported at a frequency of 0.000065 in the European (Non Finnish) population of the Genome Aggregation Database. Based on the evidence and due to the potential impact of frameshift variants, the p.Arg317GlufsTer35 is classified as pathogenic for Marinesco-Sjogren syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae	RCV000778754	SCV001213280	pathogenic	Marinesco-Sjögren syndrome	2023-09-17	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Arg317Glufs*35) in the SIL1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 145 amino acid(s) of the SIL1 protein. This variant is present in population databases (rs767943814, gnomAD 0.007%). This premature translational stop signal has been observed in individuals with Marinesco-Sjogren syndrome (PMID: 16282977, 24176978). This variant is also known as 947_948insT, L316fs. ClinVar contains an entry for this variant (Variation ID: 631958). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown.
Baylor Genetics	RCV000778754	SCV001529344	pathogenic	Marinesco-Sjögren syndrome	2018-02-02	criteria provided, single submitter	clinical testing	This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868]. This variant has been previously reported in patients with Marinesco-Sjoegren syndrome [PMID 16282977]
Revvity Omics, Revvity	RCV000778754	SCV002021256	pathogenic	Marinesco-Sjögren syndrome	2019-10-04	criteria provided, single submitter	clinical testing