ClinVar Miner

Submissions for variant NM_001164508.2(NEB):c.19993C>T (p.Pro6665Ser)

gnomAD frequency: 0.00008  dbSNP: rs751724804
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000641343 SCV000762984 likely benign Nemaline myopathy 2 2025-01-20 criteria provided, single submitter clinical testing
AiLife Diagnostics, AiLife Diagnostics RCV002223235 SCV002501698 uncertain significance not provided 2021-07-16 criteria provided, single submitter clinical testing
Revvity Omics, Revvity RCV002223235 SCV003811622 uncertain significance not provided 2019-10-16 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV003230562 SCV003929202 uncertain significance not specified 2023-04-06 criteria provided, single submitter clinical testing Variant summary: NEB c.19993C>T (p.Pro6665Ser) results in a non-conservative amino acid change in the encoded protein sequence. Three of four in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 227568 control chromosomes. This frequency is not significantly higher than estimated for a pathogenic variant in NEB causing Nemaline Myopathy 2 (4.4e-05 vs 0.0035), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.19993C>T in individuals affected with Nemaline Myopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. Four ClinVar submitters (evaluation after 2014) have reported the variant with conflicting assessments (VUS, n = 3; likely benign, n = 1). Based on the evidence outlined above, the variant was classified as uncertain significance.
Ambry Genetics RCV003303030 SCV003976562 uncertain significance Inborn genetic diseases 2023-05-09 criteria provided, single submitter clinical testing The c.14890C>T (p.P4964S) alteration is located in exon 103 (coding exon 101) of the NEB gene. This alteration results from a C to T substitution at nucleotide position 14890, causing the proline (P) at amino acid position 4964 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Natera, Inc. RCV000641343 SCV001460617 uncertain significance Nemaline myopathy 2 2020-01-17 no assertion criteria provided clinical testing

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