Submissions for variant NM_017780.4(CHD7):c.1803_1806del (p.Lys602fs)

dbSNP: rs1554588671

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000627640	SCV000748640	pathogenic	not provided	2018-04-24	criteria provided, single submitter	clinical testing	The c.1803_1806delGAAA variant in the CHD7 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1803_1806delGAAA variant causes a frameshift starting with codon Lysine 602, changes this amino acid to a Threonine residue, and creates a premature Stop codon at position 5 of the new reading frame, denoted p.Lys602ThrfsX5. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1803_1806delGAAA variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.1803_1806delGAAA as a pathogenic variant.
Invitae	RCV000802920	SCV000942769	pathogenic	CHARGE association	2018-08-03	criteria provided, single submitter	clinical testing	Loss-of-function variants in CHD7 are known to be pathogenic (PMID: 22461308, 25077900). This variant has not been reported in the literature in individuals with CHD7-related disease. ClinVar contains an entry for this variant (Variation ID: 524142). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Lys602Thrfs*5) in the CHD7 gene. It is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic.