Submissions for variant NM_024577.3(SH3TC2):c.279G>A (p.Lys93=) (rs776221160)

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Total submissions: 2

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV000200652	SCV000253933	pathogenic	Charcot-Marie-Tooth disease type 4	2019-05-21	criteria provided, single submitter	clinical testing	This sequence change affects codon 93 of the SH3TC2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the SH3TC2 protein. This variant also falls at the last nucleotide of exon 3 of the SH3TC2 coding sequence, which is part of the consensus splice site for this exon. This variant is present in population databases (rs776221160, ExAC 0.003%). This variant has been observed on the opposite chromosome (in trans) from or in combination with a pathogenic variant in individuals affected with Charcot-Marie-Tooth disease type 4 (PMID: 21291453, 27231023). This finding is consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. ClinVar contains an entry for this variant (Variation ID: 216120). Experimental studies have shown that this sequence change interferes with splicing of intron 3 in vitro (PMID: 22950825). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). For these reasons, this variant has been classified as Pathogenic.
Inherited Neuropathy Consortium	RCV000789577	SCV000928933	uncertain significance	Charcot-Marie-Tooth disease		no assertion criteria provided	literature only

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