ClinVar Miner

Submissions for variant NM_001164508.2(NEB):c.3127_3129dup (p.Asn1043dup)

dbSNP: rs1288870299
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000641355 SCV000762996 likely pathogenic Nemaline myopathy 2 2024-11-03 criteria provided, single submitter clinical testing This variant, c.3127_3129dup, results in the insertion of 1 amino acid(s) of the NEB protein (p.Asn1043dup), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (no rsID available, gnomAD 0.006%). This variant has been observed in individual(s) with nemaline myopathy (internal data). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 534006). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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.
Fulgent Genetics, Fulgent Genetics RCV002477410 SCV002786726 uncertain significance Nemaline myopathy 2; Arthrogryposis multiplex congenita 6 2022-04-18 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV005253021 SCV005907955 uncertain significance Nemaline myopathy 2025-03-21 criteria provided, single submitter curation The p.Asn1043dup variant in NEB has not been reported in the literature in individuals with nemaline myopathy, but has been identified in 0.007% (4/60030) of Latino/Admixed American chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP ID: rs1288870299). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. This variant has also been reported in ClinVar (Variation ID: 534006) and has been interpreted as likely pathogenic by Invitae and a variant of uncertain significance by Fulgent Genetics and Natera, Inc. This variant is an insertion of one amino acid at position 1043 and is not predicted to alter the protein reading-frame. It is unclear if this deletion will impact the protein. In summary, the clinical significance of the p.Asn1043dup variant is uncertain. ACMG/AMP Criteria applied:PM2_supporting, PM4_supporting (Richards 2015).
Natera, Inc. RCV000641355 SCV002077758 uncertain significance Nemaline myopathy 2 2019-11-11 no assertion criteria provided clinical testing

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