ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.3874A>G (p.Ser1292Gly) (rs1553521537)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000667109 SCV000791507 uncertain significance Nemaline myopathy 2 2017-05-19 criteria provided, single submitter clinical testing
Invitae RCV000667109 SCV001207804 likely pathogenic Nemaline myopathy 2 2019-05-17 criteria provided, single submitter clinical testing This sequence change replaces serine with glycine at codon 1292 of the NEB protein (p.Ser1292Gly). The serine residue is moderately conserved and there is a small physicochemical difference between serine and glycine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to segregate with disease and in trans (on the opposite chromosome) from a pathogenic variant in NEB in a family affected with nemaline myopathy 2 (PMID: 25473036). ClinVar contains an entry for this variant (Variation ID: 551937). 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: "Not available"; Align-GVGD: "Class C0"). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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