ClinVar

Description

The Gln907Lys variant has not been reported in the literature but has been detec ted in 2/90 Hispanic cardiomyopathy probands tested by our laboratory. Because h ealthy control information is unavailable for this population we are unable to e xclude that this variant is common and therefore benign. In one of the families, the variant was present in 3 affected individuals, whcih is consistent with a p athogenic role. However, glutamine (Gln) at amino acid position 907 is conserved in mammals and chicken but not in evolutionary distant species (zebrafish fish carries a glycine), reducing the likelihood that the change is pathogenic. In ad dition, computational predictions are inconsistent. Three tools (AlignGVGD, SIF T, MAPP) predict that the variant is deleterious but their accuracy is unknown. In contrast, the variant was predicted to be benign using a novel tool, which wa s validated by our laboratory using a set of cardiomyopathy variants with well-e stablished clinical significance. This tool's benign prediction is estimated to be correct 89% of the time (Jordan 2011). In summary, additional data (healthy c ontrol studies and familial segregation) are needed to determine the clinical si gnificance of this variant.