Submissions for variant NM_001415.4(EIF2S3):c.1394_1397del (p.Ile465fs)

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Total submissions: 4

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Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Experimental Endocrinology, Slovak Academy of Sciences	RCV000408900	SCV000321299	pathogenic	MEHMO syndrome	2016-10-07	criteria provided, single submitter	clinical testing	found in 3 independent MEHMO patients, not found in ExAC, functional study confirms effect on eIF2 function
GeneDx	RCV000482525	SCV000571705	likely pathogenic	not provided	2016-09-30	criteria provided, single submitter	clinical testing	The c.1394_1397delTCAA variant in the EIF2S3 gene has been reported previously in a family segregating a form of syndromic X-linked intellectual disability characterized by neonatal hypoglycemia, severe microcephaly, developmental delay, micropenis, epileptic seizures and early death (Moortgat et al., 2016). In this family, the c.1394_1397delTCAA variant was present in three obligate carrier female relatives and absent in three healthy male relatives, however, no affected male relatives were available for testing (Moorgat et al., 2016). The c.1394_1397delTCAA variant causes a frameshift starting with codon Isoleucine 465, changes this amino acid to a Serine residue, and creates a premature Stop codon at position 4 of the new reading frame, denoted p.Ile465SerfsX4. This variant is predicted to cause loss of normal protein function through protein truncation. The c.1394_1397delTCAA variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Therefore, we interpret c.1394_1397delTCAA variant as a likely pathogenic variant.
Clinical Genetics and Genomics, Karolinska University Hospital	RCV000482525	SCV001449850	pathogenic	not provided	2016-05-20	criteria provided, single submitter	clinical testing
OMIM	RCV000408900	SCV000324802	pathogenic	MEHMO syndrome	2018-01-18	no assertion criteria provided	literature only

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