Submissions for variant NM_198129.4(LAMA3):c.9511+1G>A

gnomAD frequency: 0.00001  dbSNP: rs1296034886

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Counsyl	RCV000667395	SCV000791832	pathogenic	Junctional epidermolysis bullosa gravis of Herlitz	2017-05-24	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000667395	SCV000919566	pathogenic	Junctional epidermolysis bullosa gravis of Herlitz	2017-09-18	criteria provided, single submitter	clinical testing	Variant summary: The LAMA3 c.4684+1G>A variant (also known as 4651+1G>A) involves the alteration of a conserved intronic nucleotide. One in silico tool predicts a damaging outcome for this variant. 4/5 splice prediction tools predict the complete loss of a canonical splice donor site. These predictions have been confirmed by immunoblotting of cell lysates from cultured keratinocytes derived from a patient showing the amount of chain expressed by the patient was <2% of normal (Gostynska_2017). This variant was found in 1/246262 control chromosomes at a frequency of 0.0000041, which does not exceed the estimated maximal expected allele frequency of a pathogenic LAMA3 variant (0.0004523). In addition, the variant has been reported in multiple affected individuals in the literature. Taken together, this variant is classified as pathogenic.