TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14302	43129;43130;43131	chr2:178633455;178633454;178633453	chr2:179498182;179498181;179498180
N2AB	12661	38206;38207;38208	chr2:178633455;178633454;178633453	chr2:179498182;179498181;179498180
N2A	11734	35425;35426;35427	chr2:178633455;178633454;178633453	chr2:179498182;179498181;179498180
N2B	5237	15934;15935;15936	chr2:178633455;178633454;178633453	chr2:179498182;179498181;179498180
Novex-1	5362	16309;16310;16311	chr2:178633455;178633454;178633453	chr2:179498182;179498181;179498180
Novex-2	5429	16510;16511;16512	chr2:178633455;178633454;178633453	chr2:179498182;179498181;179498180
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-93
• Domain position: 72
• Structural Position: 157
• Q(SASA): 0.4145
• 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
D/G	None	None	0.955	D	0.7	0.373	0.403609169532	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
D/N	None	None	0.977	N	0.733	0.292	0.347659731818	gnomAD-4.0.0	1.59235E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85969E-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
D/A	0.4152	ambiguous	0.408	ambiguous	-0.209	Destabilizing	0.955	D	0.729	prob.delet.	N	0.50917099	None	None	N
D/C	0.8581	likely_pathogenic	0.8271	pathogenic	0.052	Stabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
D/E	0.4371	ambiguous	0.4142	ambiguous	-0.477	Destabilizing	0.977	D	0.571	neutral	N	0.487524179	None	None	N
D/F	0.7963	likely_pathogenic	0.7846	pathogenic	0.334	Stabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
D/G	0.585	likely_pathogenic	0.5914	pathogenic	-0.668	Destabilizing	0.955	D	0.7	prob.neutral	D	0.652660443	None	None	N
D/H	0.5182	ambiguous	0.5264	ambiguous	-0.026	Destabilizing	1.0	D	0.845	deleterious	D	0.538208368	None	None	N
D/I	0.5319	ambiguous	0.5056	ambiguous	1.039	Stabilizing	0.998	D	0.881	deleterious	None	None	None	None	N
D/K	0.7788	likely_pathogenic	0.7712	pathogenic	-0.303	Destabilizing	0.995	D	0.791	deleterious	None	None	None	None	N
D/L	0.6358	likely_pathogenic	0.621	pathogenic	1.039	Stabilizing	0.995	D	0.851	deleterious	None	None	None	None	N
D/M	0.8441	likely_pathogenic	0.831	pathogenic	1.577	Stabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
D/N	0.1387	likely_benign	0.1314	benign	-0.86	Destabilizing	0.977	D	0.733	prob.delet.	N	0.503171115	None	None	N
D/P	0.9841	likely_pathogenic	0.9858	pathogenic	0.65	Stabilizing	0.998	D	0.857	deleterious	None	None	None	None	N
D/Q	0.6992	likely_pathogenic	0.6887	pathogenic	-0.549	Destabilizing	0.998	D	0.78	deleterious	None	None	None	None	N
D/R	0.7535	likely_pathogenic	0.7589	pathogenic	-0.294	Destabilizing	0.995	D	0.887	deleterious	None	None	None	None	N
D/S	0.2379	likely_benign	0.2334	benign	-1.297	Destabilizing	0.635	D	0.341	neutral	None	None	None	None	N
D/T	0.4908	ambiguous	0.4786	ambiguous	-0.883	Destabilizing	0.99	D	0.791	deleterious	None	None	None	None	N
D/V	0.3732	ambiguous	0.3444	ambiguous	0.65	Stabilizing	0.993	D	0.854	deleterious	N	0.475347172	None	None	N
D/W	0.9658	likely_pathogenic	0.9671	pathogenic	0.367	Stabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
D/Y	0.395	ambiguous	0.3762	ambiguous	0.586	Stabilizing	1.0	D	0.873	deleterious	D	0.558243328	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.