They tend to be major, but only 11 of 19 (11 of 17 that exist) go from one geo extreme to the other. Sorry highway numbers are a hobby of mine (yes I know strange hobby).
5 ^: Mexico to Canada
10 ^: Pacific to Atlantic
15 ^: Mexico to Canada
20: Mid-Texas to Mid-South Carolina
25: Southern Texas to Wyoming
30: Texas to Arkansas
35 ^: Mexico to almost Canada
40 ^: Eastern California, to Eastern North Carolina
45: Entirely in Texas
50: N/A
55 ^: Gulf of Mexico to Great Lakes
60: N/A
65 ^: Gulf of Mexico to Great Lakes
70: Utah to Maryland
75 ^: Southern Florida to northern Michigan
80 ^: San Francisco to New York
85: Mid-Alabama to Mid-Virginia
90 ^: Seattle to Boston (longest in the country)
95 ^: Maine to Florida