Table 3 Statistical analysis of the distribution of the variants across the protein sequence.

		ATM	BRCA1	BRCA2	MUTYH
COSMIC Metastatic/Primary	D	0.078415	0.25953	0.15202	0.25
COSMIC Metastatic/Primary	P-value	0.3615	0.1195	0.1309	0.9853
ClinVar Pathogenic/VUS	D	0.029031	0.033094	0.052161	0.089771
ClinVar Pathogenic/VUS	P-value	0.6966	0.1733	0.000167	0.5426
ClinVar Pathogenic/Benign	D	0.19303	0.076781	0.15275	0.36809
ClinVar Pathogenic/Benign	P-value	0.1771	0.4802	0.0004421	0.1726
ClinVar VUS/Benign	D	0.19993	0.054376	0.11721	0.39808
ClinVar VUS/Benign	P-value	0.1361	0.8739	0.01295	0.08924

Statistical significance of the differences between the density distributions in Fig. 6, as calculated using the GLDEX package (https://CRAN.R-project.org/package=GLDEX). Statistically significant differences (shown in bold) are indicated where the P-value is less than 0.05.

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