Submissions for variant NM_004387.4(NKX2-5):c.443del (p.Ala148fs)

dbSNP: rs876661381

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000223727	SCV000567521	pathogenic	not provided	2015-08-05	criteria provided, single submitter	clinical testing	Although the c.443delC deletion in the NKX2-5 gene has not been reported to our knowledge, thisvariant causes a shift in reading frame starting at codon Alanine 148, changing it to a Glycine andcreating a premature stop codon at position 28 of the new reading frame, denoted p.Ala148GlyfsX28. Thisdeletion is expected to result in an abnormal, truncated protein product. Additionally, other truncatingvariants in the NKX2-5 gene downstream of this deletion have been reported in the Human GeneMutation Database in association with disease (Stenson et al., 2014). Furthermore, the c.443delC variant was not observed in approximately 6,500 individuals of European and African American ancestry in theNHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations.In summary, c.443delC in the NKX2-5 gene is interpreted as a pathogenic variant.
Stanford Center for Inherited Cardiovascular Disease, Stanford University	RCV000223727	SCV000280404	likely pathogenic	not provided	2015-09-17	no assertion criteria provided	clinical testing	Note this variant was found in clinical genetic testing performed by one or more labs who may also submit to ClinVar. Thus any internal case data may overlap with the internal case data of other labs. The interpretation reviewed below is that of the Stanford Center for Inherited Cardiovascular Disease