Rashi and Targum Yonasan: It refers to Avodah Zarah, which the Torah calls "D'var Hashem" because the warning against Avodah-Zarah ("Anochi" and "Lo Yih'yeh l'cha") they heard directly from Hashem, ¹ as opposed to the other Mitzvos, which they heard from Moshe (and because it was the first Mitzvah that Hashem commanded Yisrael at Sinai - Targum Yonasan).

B'rachos, 24b: It refers (even) to someone who walks through unclean alleyways and recites Keri'as Sh'ma. ²

Sanhedrin, 99a #1: It refers to someone who claims that Torah is not from Heaven - and even if he says that all of it is from Heaven with the exception of one Pasuk, which Moshe said of his own accord, ³ or even just one nuance, one Kal va'Chomer ⁴ or one Gezeirah Shavah.

Sanhedrin, 99a #2: It refers to an Apikores - who claims that the Rabbanan learn for themselves and are of no use to the people.

Sanhedrin, 99a #3: It refers to someone who interprets the Torah in his own way, ⁵ not in accordance with the principles via which the Torah is explained. ⁶

Sanhedrin, 99a #4: It refers a. to someone who learns Torah but declines to teach it; ⁷ b. to someone who does not attach sufficient importance to the Mishnayos that he has learnt to revise them ⁸ and c. to someone who is able to learn Torah but fails to do so. ⁹

Rashi: It includes someone who worships Avodah-Zarah. ¹

Targum Yonasan and Sanhedrin, 99a: It includes someone who did not perform the B'ris Milah. ²

Yerushalmi Sanhedrin, 10:1: It includes someone who denies just one Pasuk in the Torah - such as "Achos Lotan Timna" ³ (Vayishlach, Bereishis, 36:22), one Targum - such as "Vayikra lo Y'gar Sahadusa" (Vayeitzei, Bereishis, 31:47), or one Kal va'Chomer - such as "Ki Shiv'asayim Yukam Kayin" (Bereishis, 4:24)

Targum Yonasan and Shevu'os, 13a: To teach us that he is Chayav Kareis in both this world and the next. ¹

Seforno (by implication): Because that is the way that people speak. ²

Oznayim la'Torah: Bearing in mind that the previous Pasuk is discusing someone who serves Avodah Zarah and denies the existence of Hashem whereas the current Pasuk is discussing someone who believes that Hashem exists but denies His Torah - like the modern-day reformers - the former are more likely to realize their mistake and do Teshuvah, than the latter, who believe in Hashem, but think that He makes demand of them. Hence the latter are more likely to die witjhout doing Teshuvah and lose their portion in the world to come. ¹ ,

Rashi (citing Shevu'os, 13a): It implies that he is Chayav Kareis only if he did not do Teshuvah. ¹

Ramban #2: It implies that 'He will receive his punishment'. ²

Ramban #3 (citing Pirkei Derech Eretz): It implies that he will die together with his sin - and will continue to suffer after death. ³

Seforno: It implies that his sin remains with him until he dies. ⁴

Yerushalmi Pe?ah, 1:1: It implies that his sin will remin with him even after he dies ? that the sin of Avodah Zarah is one of those sins that are punished in this world, but the main punishment is due in the world to come.