ClinVar Miner

Submissions for variant NM_001271208.2(NEB):c.23881C>T (p.Pro7961Ser) (rs193224180)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000174649 SCV000225982 likely benign not specified 2015-03-23 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000174649 SCV000272197 uncertain significance not specified 2015-11-03 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The p.Pro7961Ser va riant in NEB has not been previously reported in individuals with myopathy, but has been identified in 0.15% (97/66646) of European chromosomes by the Exome Agg regation Consortium (ExAC, http://exac.broadinstitute.org; dbSNP rs193224180). C omputational prediction tools and conservation analysis do not provide strong su pport for or against an impact to the protein. In summary, while the clinical si gnificance of the p.Pro7961Ser variant is uncertain, these data suggest that it is more likely to be benign.
Invitae RCV001080323 SCV000640729 likely benign Nemaline myopathy 2 2020-12-05 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000556596 SCV001152432 uncertain significance not provided 2016-05-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001080323 SCV001291480 uncertain significance Nemaline myopathy 2 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Natera, Inc. RCV001080323 SCV001454443 uncertain significance Nemaline myopathy 2 2019-11-11 no assertion criteria provided clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000556596 SCV001554126 uncertain significance not provided no assertion criteria provided clinical testing The NEB p.Pro7926Ser variant was not identified in the literature nor was it identified in Cosmic. The variant was identified in dbSNP (ID: rs193224180), ClinVar (classified as likely benign by EGL Genetics and as a VUS by Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine and Invitae for nemaline myopathy 2) and LOVD 3.0. The variant was identified in control databases in 316 of 280356 chromosomes at a frequency of 0.001127 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database Feb 27, 2017). The variant was observed in the following populations: European (non-Finnish) in 260 of 128302 chromosomes (freq: 0.002026), Latino in 38 of 35298 chromosomes (freq: 0.001077), Other in 6 of 7122 chromosomes (freq: 0.000843), African in 8 of 24192 chromosomes (freq: 0.000331), European (Finnish) in 3 of 25010 chromosomes (freq: 0.00012) and Ashkenazi Jewish in 1 of 10348 chromosomes (freq: 0.000097); it was not observed in the East Asian and South Asian populations. The p.Pro7926 residue is conserved across mammals and other organisms, and four out of five computational analyses (PolyPhen-2, SIFT, BLOSUM, MutationTaster) suggest that the variant may impact the protein; however, this information is not predictive enough to assume pathogenicity. The variant occurs outside of the splicing consensus sequence and 3 of 4 in silico or computational prediction software programs (MaxEntScan, NNSPLICE, GeneSplicer) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time. This variant is classified as a variant of uncertain significance.

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