ClinVar Miner

Submissions for variant NM_024577.3(SH3TC2):c.1840G>A (p.Asp614Asn) (rs201789838)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000522493 SCV000619630 uncertain significance not provided 2017-08-03 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the SH3TC2 gene. The D614N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D614N variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D614N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. However, this substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000797406 SCV000936960 uncertain significance Charcot-Marie-Tooth disease type 4 2018-09-11 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with asparagine at codon 614 of the SH3TC2 protein (p.Asp614Asn). The aspartic acid residue is moderately conserved and there is a small physicochemical difference between aspartic acid and asparagine. This variant is present in population databases (rs201789838, ExAC 0.003%). This variant has not been reported in the literature in individuals with SH3TC2-related disease. ClinVar contains an entry for this variant (Variation ID: 450992). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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