ClinVar Miner

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

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,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 2019-01-15 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the SIL1 gene (p.Arg317Glufs*35). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 145 amino acids of the SIL1 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the ExAC database. This variant has been observed in the homozygous or compound heterozygous state in several individuals affected with Marinesco-Sjogren syndrome (PMID: 16282977, 24176978). This variant is also known as 947_948insT, L316fs in the literature. Experimental studies and prediction algorithms are not available for this variant, and the functional significance of the affected amino acid(s) is currently unknown. For these reasons, this variant has been classified as Pathogenic.

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