Submissions for variant NM_170606.3(KMT2C):c.6604C>A (p.Pro2202Thr)

gnomAD frequency: 0.00003  dbSNP: rs760297553

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
New York Genome Center	RCV001839291	SCV002099276	uncertain significance	Kleefstra syndrome 2	2021-04-09	criteria provided, single submitter	clinical testing	The c.6604C>A (p.Pro2202Thr) variant identified in the KMT2C gene substitutes a conserved Proline for Threonine at amino acid 2202/4912 (exon 36/59). This variant is found with low frequency in gnomAD(v3.1.1) (3 heterozygotes, 0 homozygotes; allele frequency: 1.97e-5) suggesting it is not a common benign variant in the populations represented in that database. In silico algorithms do not agree on the effect of this variant, as it is predicted both Damaging (SIFT; score:0.001) and Benign (REVEL; score: 0.503) to the function of the canonical transcript. This variant is absent from ClinVar and to our current knowledge has not been reported in affected individuals in the literature. The p.Pro2202 residue is not within a mapped domain of KMT2C (UniProtKB:Q8NEZ4). Given the lack of compelling evidence for its pathogenicity, the c.6604C>A (p.Pro2202Thr) variant identified in the KMT2C gene is reported as a Variant of Uncertain Significance.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002034710	SCV002152528	benign	not provided	2023-07-07	criteria provided, single submitter	clinical testing