ClinVar Miner

Submissions for variant NM_000368.4(TSC1):c.1921C>T (p.Pro641Ser) (rs374222196)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163665 SCV000214237 benign Hereditary cancer-predisposing syndrome 2018-06-28 criteria provided, single submitter clinical testing Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;In silico models in agreement (benign);Other data supporting benign classification
GeneDx RCV000725780 SCV000243467 benign not provided 2019-07-05 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 24728327)
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000725780 SCV000339329 uncertain significance not provided 2016-02-12 criteria provided, single submitter clinical testing
Invitae RCV001080054 SCV000552288 benign Tuberous sclerosis 1 2020-12-06 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV000725780 SCV000884752 likely benign not provided 2018-06-30 criteria provided, single submitter clinical testing The TSC1 c.1921C>T; p.Pro641Ser variant (rs374222196), to our knowledge, is not reported in the medical literature, but is listed in ClinVar (Variation ID: 135364). This variant is found in the general population with an overall allele frequency of 0.005% (13/27,7182 alleles) in the Genome Aggregation Database, and has a higher than expected frequency in the East Asian population (0.05%, 10/18,870 alleles) based on an estimated prevalence of 1 in 17,400 for TSC1-associated Tuberous Sclerosis Complex (Northrup 2015). The proline at codon 641 is moderately conserved, but computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. In addition, most pathogenic TSC1 variants are null alleles and only rarely (<5%) missense variants (Northrup 2015). Based on available information, this variant is considered to be likely benign. REFERENCES Northrup H, Koenig MK, Pearson DA, et al. Tuberous Sclerosis Complex. 1999 Jul 13 (Updated 2015 Sep 3). In: Adam MP, Ardinger HH, Pagon RA, et al., editors. GeneReviews (Internet). Seattle (WA): University of Washington, Seattle; 1993-2018. Available from: https://www.ncbi.nlm.nih.gov/books/NBK1220/.
ITMI RCV000122190 SCV000086408 not provided not specified 2013-09-19 no assertion provided reference population

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