TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33148	99667;99668;99669	chr2:178537765;178537764;178537763	chr2:179402492;179402491;179402490
N2AB	31507	94744;94745;94746	chr2:178537765;178537764;178537763	chr2:179402492;179402491;179402490
N2A	30580	91963;91964;91965	chr2:178537765;178537764;178537763	chr2:179402492;179402491;179402490
N2B	24083	72472;72473;72474	chr2:178537765;178537764;178537763	chr2:179402492;179402491;179402490
Novex-1	24208	72847;72848;72849	chr2:178537765;178537764;178537763	chr2:179402492;179402491;179402490
Novex-2	24275	73048;73049;73050	chr2:178537765;178537764;178537763	chr2:179402492;179402491;179402490
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-156
• Domain position: 48
• Structural Position: 122
• Q(SASA): 0.2837
• 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/N	None	None	1.0	D	0.679	0.39	0.225215365344	gnomAD-4.0.0	1.59135E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85843E-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	0.5672	likely_pathogenic	0.6551	pathogenic	-0.291	Destabilizing	1.0	D	0.654	neutral	None	None	None	None	N
K/C	0.8226	likely_pathogenic	0.8655	pathogenic	-0.231	Destabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	N
K/D	0.8288	likely_pathogenic	0.8542	pathogenic	-0.091	Destabilizing	1.0	D	0.743	deleterious	None	None	None	None	N
K/E	0.3356	likely_benign	0.3997	ambiguous	-0.062	Destabilizing	0.999	D	0.568	neutral	N	0.484862952	None	None	N
K/F	0.8941	likely_pathogenic	0.9194	pathogenic	-0.476	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
K/G	0.733	likely_pathogenic	0.8047	pathogenic	-0.557	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
K/H	0.3742	ambiguous	0.4276	ambiguous	-1.08	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	N
K/I	0.5214	ambiguous	0.5575	ambiguous	0.349	Stabilizing	0.996	D	0.772	deleterious	N	0.521074469	None	None	N
K/L	0.5319	ambiguous	0.5909	pathogenic	0.349	Stabilizing	0.997	D	0.675	prob.neutral	None	None	None	None	N
K/M	0.4058	ambiguous	0.4691	ambiguous	0.506	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	N
K/N	0.648	likely_pathogenic	0.703	pathogenic	0.054	Stabilizing	1.0	D	0.679	prob.neutral	D	0.522034474	None	None	N
K/P	0.9836	likely_pathogenic	0.9876	pathogenic	0.165	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
K/Q	0.1528	likely_benign	0.1935	benign	-0.212	Destabilizing	0.999	D	0.656	neutral	N	0.4968881	None	None	N
K/R	0.0819	likely_benign	0.0914	benign	-0.196	Destabilizing	0.998	D	0.531	neutral	N	0.481996006	None	None	N
K/S	0.5967	likely_pathogenic	0.6727	pathogenic	-0.546	Destabilizing	1.0	D	0.615	neutral	None	None	None	None	N
K/T	0.2859	likely_benign	0.3433	ambiguous	-0.347	Destabilizing	1.0	D	0.717	prob.delet.	N	0.462468882	None	None	N
K/V	0.4837	ambiguous	0.5244	ambiguous	0.165	Stabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
K/W	0.8841	likely_pathogenic	0.9189	pathogenic	-0.386	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
K/Y	0.8132	likely_pathogenic	0.8417	pathogenic	-0.018	Destabilizing	0.999	D	0.721	prob.delet.	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.