TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25117	75574;75575;75576	chr2:178570783;178570782;178570781	chr2:179435510;179435509;179435508
N2AB	23476	70651;70652;70653	chr2:178570783;178570782;178570781	chr2:179435510;179435509;179435508
N2A	22549	67870;67871;67872	chr2:178570783;178570782;178570781	chr2:179435510;179435509;179435508
N2B	16052	48379;48380;48381	chr2:178570783;178570782;178570781	chr2:179435510;179435509;179435508
Novex-1	16177	48754;48755;48756	chr2:178570783;178570782;178570781	chr2:179435510;179435509;179435508
Novex-2	16244	48955;48956;48957	chr2:178570783;178570782;178570781	chr2:179435510;179435509;179435508
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-134
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.0924
• Predicted PPI site: N

Reported SAVs

SNV	RS	DUET	PolyPhen-2	Condel	Rhapsody	REVEL	MVP	Source	MAF	Disease	Zygosity	Site annotation	mCSM PPI	Predicted PPI site	Comments	AFR	AMR	AMS	ASJ	EAS	EUR	FIN	MDE	NFE	SAS	OTH
Y/C	rs1559394408	None	0.005	N	0.554	0.189	0.204665344411	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0

Saturation Mutagenesis

SAV	AlphaMissense (IC)	AlphaMissense Class (IC)	AlphaMissense (N2AB)	AlphaMissense Class (N2AB)	mCSM	mCSM class	PolyPhen-2	PolyPhen-2 Class	Rhapsody	Rhapsody Class	Condel	Condel Score	Site annotation	mCSM PPI	Predicted PPI site
Y/A	0.8047	likely_pathogenic	0.8387	pathogenic	-2.615	Highly Destabilizing	0.157	N	0.631	neutral	None	None	None	None	N
Y/C	0.2961	likely_benign	0.3104	benign	-1.1	Destabilizing	0.005	N	0.554	neutral	N	0.481952892	None	None	N
Y/D	0.721	likely_pathogenic	0.7657	pathogenic	-2.109	Highly Destabilizing	0.859	D	0.747	deleterious	N	0.499803658	None	None	N
Y/E	0.9029	likely_pathogenic	0.9287	pathogenic	-2.014	Highly Destabilizing	0.726	D	0.709	prob.delet.	None	None	None	None	N
Y/F	0.1168	likely_benign	0.1192	benign	-1.125	Destabilizing	0.001	N	0.29	neutral	N	0.464674107	None	None	N
Y/G	0.7297	likely_pathogenic	0.7721	pathogenic	-2.955	Highly Destabilizing	0.726	D	0.707	prob.neutral	None	None	None	None	N
Y/H	0.4338	ambiguous	0.4812	ambiguous	-1.582	Destabilizing	0.859	D	0.683	prob.neutral	N	0.488282768	None	None	N
Y/I	0.6329	likely_pathogenic	0.684	pathogenic	-1.548	Destabilizing	0.396	N	0.694	prob.neutral	None	None	None	None	N
Y/K	0.8849	likely_pathogenic	0.9109	pathogenic	-1.606	Destabilizing	0.726	D	0.707	prob.neutral	None	None	None	None	N
Y/L	0.5295	ambiguous	0.5586	ambiguous	-1.548	Destabilizing	0.157	N	0.606	neutral	None	None	None	None	N
Y/M	0.7124	likely_pathogenic	0.7462	pathogenic	-1.065	Destabilizing	0.909	D	0.714	prob.delet.	None	None	None	None	N
Y/N	0.4561	ambiguous	0.515	ambiguous	-1.965	Destabilizing	0.859	D	0.719	prob.delet.	N	0.479417997	None	None	N
Y/P	0.967	likely_pathogenic	0.9741	pathogenic	-1.905	Destabilizing	0.89	D	0.757	deleterious	None	None	None	None	N
Y/Q	0.8114	likely_pathogenic	0.8482	pathogenic	-1.896	Destabilizing	0.89	D	0.727	prob.delet.	None	None	None	None	N
Y/R	0.8042	likely_pathogenic	0.8439	pathogenic	-1.164	Destabilizing	0.726	D	0.717	prob.delet.	None	None	None	None	N
Y/S	0.6251	likely_pathogenic	0.6824	pathogenic	-2.332	Highly Destabilizing	0.497	N	0.682	prob.neutral	N	0.475152036	None	None	N
Y/T	0.8024	likely_pathogenic	0.8383	pathogenic	-2.142	Highly Destabilizing	0.567	D	0.686	prob.neutral	None	None	None	None	N
Y/V	0.5725	likely_pathogenic	0.6115	pathogenic	-1.905	Destabilizing	0.157	N	0.647	neutral	None	None	None	None	N
Y/W	0.5397	ambiguous	0.5661	pathogenic	-0.771	Destabilizing	0.909	D	0.676	prob.neutral	None	None	None	None	N

Titin has multiple isoforms, the longest being the theoretical IC (inferred complete) isoform which contains all 363 in-frame titin exons. Here all isoform positions have been mapped onto the IC sequence, with an exception being the C-terminal of the much shorter novex-3 isoform. This contains the out of frame exon 48 which cannot be mapped to the other isoforms.