ClinVar Miner

Submissions for variant NM_000548.5(TSC2):c.4046C>T (p.Ala1349Val) (rs201979616)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000034656 SCV000243701 uncertain significance not provided 2012-03-22 criteria provided, single submitter clinical testing p.Ala1349Val (GCG>GTG): c.4046 C>T in exon 34 of the TSC2 gene. The Ala1349Val missense substitution in TSC2 has not been published as a mutation nor has it been reported as a benign polymorphism, to our knowledge. The NHLBI ESP Exome Variant Project has not identified Ala1349Val in approximately 5,000 individuals of European or African American ethnicity, indicating that it is not a common benign variant in these populations. The Ala1349Val amino acid substitution is conservative since both Alanine and Valine are uncharged non-polar amino acids, and it alters a position in the TSC2 protein that is not highly conserved across species. This substitution does not occur within known functional domains of the tuberin protein, where many pathogenic missense mutations have been identified (Northrup et al., 2011; Au et al., 2007). Multiple in-silico algorithms predict that the Ala1349Val change does not adversely affect the tuberin protein structure. These findings suggest that Ala1349Val is likely a rare benign variant; however, the possibility that Ala1349Val is disease-causing cannot be excluded at present, The variant is found in EPILEPSY panel(s).
Ambry Genetics RCV000215282 SCV000277729 uncertain significance Hereditary cancer-predisposing syndrome 2019-04-24 criteria provided, single submitter clinical testing Insufficient or conflicting evidence
Invitae RCV001081977 SCV000544338 benign Tuberous sclerosis 2 2019-12-31 criteria provided, single submitter clinical testing
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000034656 SCV000043539 variant of unknown significance not provided 2012-07-13 no assertion criteria provided research Converted during submission to Uncertain significance.
Clinical Genomics Lab,St. Jude Children's Research Hospital RCV000761016 SCV000890931 uncertain significance Retinoblastoma 2016-03-21 no assertion criteria provided clinical testing

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