ClinVar Miner

Submissions for variant NM_005902.4(SMAD3):c.206+1G>C (rs770098673)

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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000826214 SCV000967780 likely pathogenic Loeys-Dietz syndrome 2018-03-16 criteria provided, single submitter clinical testing The c.206+1G>C variant in SMAD3 has not been previously reported in individuals with clinical features of Loeys-Dietz syndrome type 3 (LDS3) or in large populat ion studies. This variant occurs in the invariant region (+/- 1,2) of the SMAD3 exon 1 splice consensus sequence and is predicted to cause altered splicing lead ing to an abnormal or absent protein. Heterozygous loss of function of the SMAD3 gene has been reported in individuals with LDS3. Although, exon 1 is not includ ed in all SMAD3 transcripts, it is present in the predominant transcript and the re is some evidence to support a role for loss of function variants in exon 1 in individuals with clinical features of LDS3 (Fitzgerald 2014). In summary, altho ugh additional studies are required to fully establish its clinical significance , the c.206+1G>C variant is likely pathogenic. ACMG/AMP criteria applied: PVS1_s trong, PM2.

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