TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20704	62335;62336;62337	chr2:178589615;178589614;178589613	chr2:179454342;179454341;179454340
N2AB	19063	57412;57413;57414	chr2:178589615;178589614;178589613	chr2:179454342;179454341;179454340
N2A	18136	54631;54632;54633	chr2:178589615;178589614;178589613	chr2:179454342;179454341;179454340
N2B	11639	35140;35141;35142	chr2:178589615;178589614;178589613	chr2:179454342;179454341;179454340
Novex-1	11764	35515;35516;35517	chr2:178589615;178589614;178589613	chr2:179454342;179454341;179454340
Novex-2	11831	35716;35717;35718	chr2:178589615;178589614;178589613	chr2:179454342;179454341;179454340
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-38
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.1628
• 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
H/D	rs1553641034	None	0.852	N	0.703	0.314	0.36256342048	gnomAD-4.0.0	4.79085E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	3.47464E-04	2.69898E-06	0	3.31378E-05
H/R	rs770845631	-2.203	0.959	N	0.689	0.264	0.305086939656	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
H/R	rs770845631	-2.203	0.959	N	0.689	0.264	0.305086939656	gnomAD-4.0.0	1.59231E-06	None	None	None	None	N	None	0	2.2877E-05	None	0	0	None	0	0	0	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
H/A	0.7089	likely_pathogenic	0.7313	pathogenic	-2.008	Highly Destabilizing	0.969	D	0.695	prob.neutral	None	None	None	None	N
H/C	0.3949	ambiguous	0.4434	ambiguous	-1.186	Destabilizing	0.999	D	0.699	prob.neutral	None	None	None	None	N
H/D	0.7617	likely_pathogenic	0.786	pathogenic	-1.963	Destabilizing	0.852	D	0.703	prob.neutral	N	0.481576639	None	None	N
H/E	0.7865	likely_pathogenic	0.8076	pathogenic	-1.777	Destabilizing	0.939	D	0.644	neutral	None	None	None	None	N
H/F	0.3973	ambiguous	0.4374	ambiguous	0.012	Stabilizing	0.884	D	0.719	prob.delet.	None	None	None	None	N
H/G	0.8636	likely_pathogenic	0.8737	pathogenic	-2.374	Highly Destabilizing	0.863	D	0.69	prob.neutral	None	None	None	None	N
H/I	0.4447	ambiguous	0.4779	ambiguous	-0.91	Destabilizing	0.991	D	0.726	prob.delet.	None	None	None	None	N
H/K	0.7511	likely_pathogenic	0.7267	pathogenic	-1.555	Destabilizing	0.939	D	0.705	prob.neutral	None	None	None	None	N
H/L	0.2905	likely_benign	0.3156	benign	-0.91	Destabilizing	0.92	D	0.724	prob.delet.	N	0.425549998	None	None	N
H/M	0.6549	likely_pathogenic	0.6786	pathogenic	-1.106	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
H/N	0.3247	likely_benign	0.3688	ambiguous	-2.062	Highly Destabilizing	0.061	N	0.275	neutral	N	0.433284047	None	None	N
H/P	0.954	likely_pathogenic	0.9568	pathogenic	-1.27	Destabilizing	0.996	D	0.693	prob.neutral	N	0.512419621	None	None	N
H/Q	0.5619	ambiguous	0.6039	pathogenic	-1.632	Destabilizing	0.959	D	0.706	prob.neutral	N	0.451869808	None	None	N
H/R	0.4842	ambiguous	0.4988	ambiguous	-1.834	Destabilizing	0.959	D	0.689	prob.neutral	N	0.457390271	None	None	N
H/S	0.6268	likely_pathogenic	0.6621	pathogenic	-2.159	Highly Destabilizing	0.863	D	0.673	neutral	None	None	None	None	N
H/T	0.6103	likely_pathogenic	0.6586	pathogenic	-1.877	Destabilizing	0.939	D	0.697	prob.neutral	None	None	None	None	N
H/V	0.4172	ambiguous	0.4486	ambiguous	-1.27	Destabilizing	0.939	D	0.732	prob.delet.	None	None	None	None	N
H/W	0.5533	ambiguous	0.5475	ambiguous	0.491	Stabilizing	0.998	D	0.66	neutral	None	None	None	None	N
H/Y	0.1942	likely_benign	0.2393	benign	0.213	Stabilizing	0.134	N	0.311	neutral	N	0.434497555	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.