TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26312	79159;79160;79161	chr2:178567198;178567197;178567196	chr2:179431925;179431924;179431923
N2AB	24671	74236;74237;74238	chr2:178567198;178567197;178567196	chr2:179431925;179431924;179431923
N2A	23744	71455;71456;71457	chr2:178567198;178567197;178567196	chr2:179431925;179431924;179431923
N2B	17247	51964;51965;51966	chr2:178567198;178567197;178567196	chr2:179431925;179431924;179431923
Novex-1	17372	52339;52340;52341	chr2:178567198;178567197;178567196	chr2:179431925;179431924;179431923
Novex-2	17439	52540;52541;52542	chr2:178567198;178567197;178567196	chr2:179431925;179431924;179431923
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-79
• Domain position: 27
• Structural Position: 28
• Q(SASA): 0.9156
• 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
L/I	None	None	0.003	N	0.193	0.046	0.16115917748	gnomAD-4.0.0	1.59337E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86231E-06	0	0
L/P	None	None	0.662	N	0.382	0.18	0.62999039529	gnomAD-4.0.0	2.73845E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59956E-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
L/A	0.1055	likely_benign	0.1146	benign	-0.389	Destabilizing	0.007	N	0.149	neutral	None	None	None	None	N
L/C	0.395	ambiguous	0.3939	ambiguous	-0.563	Destabilizing	0.991	D	0.273	neutral	None	None	None	None	N
L/D	0.4804	ambiguous	0.4606	ambiguous	-0.207	Destabilizing	0.39	N	0.377	neutral	None	None	None	None	N
L/E	0.1816	likely_benign	0.1686	benign	-0.314	Destabilizing	0.002	N	0.2	neutral	None	None	None	None	N
L/F	0.1413	likely_benign	0.1414	benign	-0.564	Destabilizing	0.772	D	0.283	neutral	N	0.488218819	None	None	N
L/G	0.2814	likely_benign	0.2861	benign	-0.509	Destabilizing	0.345	N	0.34	neutral	None	None	None	None	N
L/H	0.159	likely_benign	0.1606	benign	0.09	Stabilizing	0.873	D	0.262	neutral	N	0.49579673	None	None	N
L/I	0.0892	likely_benign	0.0912	benign	-0.205	Destabilizing	0.003	N	0.193	neutral	N	0.490217552	None	None	N
L/K	0.1153	likely_benign	0.1242	benign	-0.221	Destabilizing	0.209	N	0.258	neutral	None	None	None	None	N
L/M	0.0998	likely_benign	0.1029	benign	-0.38	Destabilizing	0.818	D	0.3	neutral	None	None	None	None	N
L/N	0.243	likely_benign	0.2522	benign	0.008	Stabilizing	0.561	D	0.419	neutral	None	None	None	None	N
L/P	0.2431	likely_benign	0.2395	benign	-0.235	Destabilizing	0.662	D	0.382	neutral	N	0.496834093	None	None	N
L/Q	0.0755	likely_benign	0.0748	benign	-0.225	Destabilizing	0.017	N	0.197	neutral	None	None	None	None	N
L/R	0.1135	likely_benign	0.1114	benign	0.287	Stabilizing	0.001	N	0.148	neutral	N	0.46478039	None	None	N
L/S	0.1302	likely_benign	0.1317	benign	-0.373	Destabilizing	0.209	N	0.281	neutral	None	None	None	None	N
L/T	0.1257	likely_benign	0.1352	benign	-0.378	Destabilizing	0.345	N	0.311	neutral	None	None	None	None	N
L/V	0.0793	likely_benign	0.0795	benign	-0.235	Destabilizing	0.166	N	0.211	neutral	N	0.454411467	None	None	N
L/W	0.2673	likely_benign	0.2352	benign	-0.589	Destabilizing	0.991	D	0.251	neutral	None	None	None	None	N
L/Y	0.2899	likely_benign	0.2783	benign	-0.324	Destabilizing	0.965	D	0.33	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.