Submissions for variant NM_015335.5(MED13L):c.1300_1302del (p.Cys434del)

dbSNP: rs746994172

Total submissions: 3

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV003074785	SCV003459069	uncertain significance	Transposition of the great arteries, dextro-looped	2022-07-29	criteria provided, single submitter	clinical testing	This variant, c.1300_1302del, results in the deletion of 1 amino acid(s) of the MED13L protein (p.Cys434del), but otherwise preserves the integrity of the reading frame. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with MED13L-related conditions. This variant is present in population databases (rs746994172, gnomAD 0.007%).
PreventionGenetics, part of Exact Sciences	RCV004536576	SCV004120162	uncertain significance	MED13L-related disorder	2023-05-08	criteria provided, single submitter	clinical testing	The MED13L c.1300_1302delTGT variant is predicted to result in an in-frame deletion (p.Cys434del). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0063% of alleles in individuals of African descent in gnomAD (http://gnomad.broadinstitute.org/variant/12-116446915-CACA-C). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004700931	SCV005202168	uncertain significance	not specified	2024-07-01	criteria provided, single submitter	clinical testing	Variant summary: MED13L c.1300_1302delTGT (p.Cys434del) results in an in-frame deletion that is predicted to remove 1 amino acid from the encoded protein. The variant allele was found at a frequency of 8e-06 in 250632 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1300_1302delTGT in individuals affected with Intellectual Disability And Distinctive Facial Features With Or Without Cardiac Defects and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 2151601). Based on the evidence outlined above, the variant was classified as uncertain significance.