TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28168	84727;84728;84729	chr2:178561630;178561629;178561628	chr2:179426357;179426356;179426355
N2AB	26527	79804;79805;79806	chr2:178561630;178561629;178561628	chr2:179426357;179426356;179426355
N2A	25600	77023;77024;77025	chr2:178561630;178561629;178561628	chr2:179426357;179426356;179426355
N2B	19103	57532;57533;57534	chr2:178561630;178561629;178561628	chr2:179426357;179426356;179426355
Novex-1	19228	57907;57908;57909	chr2:178561630;178561629;178561628	chr2:179426357;179426356;179426355
Novex-2	19295	58108;58109;58110	chr2:178561630;178561629;178561628	chr2:179426357;179426356;179426355
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: Fn3-93
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.373
• 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/I	None	None	1.0	N	0.729	0.507	0.644729278666	gnomAD-4.0.0	1.59556E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43843E-05	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	0.5285	ambiguous	0.5401	ambiguous	-0.227	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
K/C	0.8125	likely_pathogenic	0.8129	pathogenic	-0.298	Destabilizing	1.0	D	0.721	prob.delet.	None	None	None	None	N
K/D	0.8938	likely_pathogenic	0.9079	pathogenic	-0.126	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
K/E	0.5882	likely_pathogenic	0.5792	pathogenic	-0.125	Destabilizing	0.999	D	0.588	neutral	N	0.513840986	None	None	N
K/F	0.9567	likely_pathogenic	0.9588	pathogenic	-0.555	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
K/G	0.6062	likely_pathogenic	0.6329	pathogenic	-0.438	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/H	0.4946	ambiguous	0.4854	ambiguous	-0.911	Destabilizing	1.0	D	0.633	neutral	None	None	None	None	N
K/I	0.8468	likely_pathogenic	0.8591	pathogenic	0.252	Stabilizing	1.0	D	0.729	prob.delet.	N	0.493360607	None	None	N
K/L	0.784	likely_pathogenic	0.8016	pathogenic	0.252	Stabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
K/M	0.6594	likely_pathogenic	0.6643	pathogenic	0.385	Stabilizing	1.0	D	0.628	neutral	None	None	None	None	N
K/N	0.7786	likely_pathogenic	0.7903	pathogenic	0.099	Stabilizing	1.0	D	0.737	prob.delet.	N	0.466809654	None	None	N
K/P	0.8587	likely_pathogenic	0.8849	pathogenic	0.121	Stabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	N
K/Q	0.2686	likely_benign	0.262	benign	-0.214	Destabilizing	1.0	D	0.727	prob.delet.	N	0.4959675	None	None	N
K/R	0.0755	likely_benign	0.0748	benign	-0.075	Destabilizing	0.999	D	0.539	neutral	N	0.518518874	None	None	N
K/S	0.6273	likely_pathogenic	0.6351	pathogenic	-0.463	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	N
K/T	0.5752	likely_pathogenic	0.6021	pathogenic	-0.311	Destabilizing	1.0	D	0.717	prob.delet.	N	0.475835328	None	None	N
K/V	0.744	likely_pathogenic	0.7721	pathogenic	0.121	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
K/W	0.9385	likely_pathogenic	0.9356	pathogenic	-0.476	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
K/Y	0.8752	likely_pathogenic	0.8741	pathogenic	-0.097	Destabilizing	1.0	D	0.707	prob.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.