TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2649	8170;8171;8172	chr2:178771382;178771381;178771380	chr2:179636109;179636108;179636107
N2AB	2649	8170;8171;8172	chr2:178771382;178771381;178771380	chr2:179636109;179636108;179636107
N2A	2649	8170;8171;8172	chr2:178771382;178771381;178771380	chr2:179636109;179636108;179636107
N2B	2603	8032;8033;8034	chr2:178771382;178771381;178771380	chr2:179636109;179636108;179636107
Novex-1	2603	8032;8033;8034	chr2:178771382;178771381;178771380	chr2:179636109;179636108;179636107
Novex-2	2603	8032;8033;8034	chr2:178771382;178771381;178771380	chr2:179636109;179636108;179636107
Novex-3	2649	8170;8171;8172	chr2:178771382;178771381;178771380	chr2:179636109;179636108;179636107

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-16
• Domain position: 29
• Structural Position: 45
• Q(SASA): 0.7921
• 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
K/E	rs769037510	0.197	None	N	0.107	0.096	0.194818534648	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.8E-06	0
K/R	rs745433704	0.227	0.012	N	0.319	0.11	0.381746406553	gnomAD-2.1.1	3.98E-06	None	None	None	None	N	None	0	0	None	0	5.45E-05	None	0	None	0	0	0
K/R	rs745433704	0.227	0.012	N	0.319	0.11	0.381746406553	gnomAD-4.0.0	4.78879E-06	None	None	None	None	N	None	0	0	None	0	5.04134E-05	None	0	0	4.4967E-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
K/A	0.1344	likely_benign	0.1306	benign	-0.072	Destabilizing	0.007	N	0.232	neutral	None	None	None	None	N
K/C	0.5743	likely_pathogenic	0.5316	ambiguous	-0.525	Destabilizing	0.864	D	0.335	neutral	None	None	None	None	N
K/D	0.1664	likely_benign	0.1757	benign	-0.291	Destabilizing	0.016	N	0.265	neutral	None	None	None	None	N
K/E	0.067	likely_benign	0.0704	benign	-0.318	Destabilizing	None	N	0.107	neutral	N	0.445992301	None	None	N
K/F	0.5556	ambiguous	0.5435	ambiguous	-0.478	Destabilizing	0.214	N	0.389	neutral	None	None	None	None	N
K/G	0.2105	likely_benign	0.2209	benign	-0.157	Destabilizing	0.016	N	0.343	neutral	None	None	None	None	N
K/H	0.2156	likely_benign	0.2074	benign	-0.252	Destabilizing	0.214	N	0.377	neutral	None	None	None	None	N
K/I	0.1842	likely_benign	0.169	benign	0.071	Stabilizing	0.029	N	0.455	neutral	D	0.549341633	None	None	N
K/L	0.2007	likely_benign	0.1902	benign	0.071	Stabilizing	None	N	0.261	neutral	None	None	None	None	N
K/M	0.1729	likely_benign	0.161	benign	-0.173	Destabilizing	0.214	N	0.377	neutral	None	None	None	None	N
K/N	0.1454	likely_benign	0.1515	benign	-0.065	Destabilizing	0.029	N	0.287	neutral	N	0.499443682	None	None	N
K/P	0.2689	likely_benign	0.2533	benign	0.044	Stabilizing	0.136	N	0.42	neutral	None	None	None	None	N
K/Q	0.0986	likely_benign	0.1015	benign	-0.206	Destabilizing	None	N	0.176	neutral	N	0.504380746	None	None	N
K/R	0.0943	likely_benign	0.0941	benign	-0.194	Destabilizing	0.012	N	0.319	neutral	N	0.513623843	None	None	N
K/S	0.1463	likely_benign	0.1447	benign	-0.427	Destabilizing	None	N	0.156	neutral	None	None	None	None	N
K/T	0.0902	likely_benign	0.0867	benign	-0.353	Destabilizing	0.012	N	0.326	neutral	N	0.490625743	None	None	N
K/V	0.1627	likely_benign	0.1534	benign	0.044	Stabilizing	0.016	N	0.362	neutral	None	None	None	None	N
K/W	0.6617	likely_pathogenic	0.6612	pathogenic	-0.585	Destabilizing	0.864	D	0.34	neutral	None	None	None	None	N
K/Y	0.4041	ambiguous	0.4038	ambiguous	-0.243	Destabilizing	0.356	N	0.425	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.