What is the meaning of "be'Yad Ramah"?
Rashi: It means 'on purpose'.
What is the definition of "Megadef'?
Rashi: "Megadef" means 'Someone who blasphemes
Rashbam: It means someone who worships Avodah-Zarah.
Targum Yonasan: It means someone who serves Avodah-Zarah and who dies without Teshuvah.
As in Yechezkel, 5:15 and in Yeshayah, Rashi (citing Kerisus, 7b):
Chazal learn from here that someone who blasphemes Hashem is subject to Kareis. Targum Yonasan:
The first Mitzvah that Hashem commanded Yisrael directly. (Refer to 15:31:1:1).
And what are the implications of "es Hashem hu Megadef"?
Seforno: It implies that, on account of the Chilul Hashem,
even Teshuvah will not atone for him until he dies.
Though the Seforno does not indicate which sin "Megadef" is referring to.