TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21921	65986;65987;65988	chr2:178583042;178583041;178583040	chr2:179447769;179447768;179447767
N2AB	20280	61063;61064;61065	chr2:178583042;178583041;178583040	chr2:179447769;179447768;179447767
N2A	19353	58282;58283;58284	chr2:178583042;178583041;178583040	chr2:179447769;179447768;179447767
N2B	12856	38791;38792;38793	chr2:178583042;178583041;178583040	chr2:179447769;179447768;179447767
Novex-1	12981	39166;39167;39168	chr2:178583042;178583041;178583040	chr2:179447769;179447768;179447767
Novex-2	13048	39367;39368;39369	chr2:178583042;178583041;178583040	chr2:179447769;179447768;179447767
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-125
• Domain position: 56
• Structural Position: 138
• Q(SASA): 0.0703
• 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/S	None	None	0.997	D	0.845	0.855	0.85411213676	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

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	0.7205	likely_pathogenic	0.7129	pathogenic	-2.607	Highly Destabilizing	0.966	D	0.733	prob.delet.	None	None	None	None	N
L/C	0.8619	likely_pathogenic	0.859	pathogenic	-2.09	Highly Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
L/D	0.9993	likely_pathogenic	0.9992	pathogenic	-3.339	Highly Destabilizing	0.999	D	0.897	deleterious	None	None	None	None	N
L/E	0.9932	likely_pathogenic	0.9931	pathogenic	-3.029	Highly Destabilizing	0.998	D	0.877	deleterious	None	None	None	None	N
L/F	0.5421	ambiguous	0.5078	ambiguous	-1.61	Destabilizing	0.993	D	0.783	deleterious	N	0.502935935	None	None	N
L/G	0.973	likely_pathogenic	0.9722	pathogenic	-3.222	Highly Destabilizing	0.998	D	0.876	deleterious	None	None	None	None	N
L/H	0.986	likely_pathogenic	0.9841	pathogenic	-2.934	Highly Destabilizing	1.0	D	0.88	deleterious	None	None	None	None	N
L/I	0.1476	likely_benign	0.1497	benign	-0.77	Destabilizing	0.966	D	0.686	prob.neutral	None	None	None	None	N
L/K	0.9859	likely_pathogenic	0.9865	pathogenic	-2.041	Highly Destabilizing	0.998	D	0.854	deleterious	None	None	None	None	N
L/M	0.1991	likely_benign	0.193	benign	-0.941	Destabilizing	0.997	D	0.774	deleterious	D	0.526649277	None	None	N
L/N	0.9938	likely_pathogenic	0.9943	pathogenic	-2.681	Highly Destabilizing	0.999	D	0.897	deleterious	None	None	None	None	N
L/P	0.9957	likely_pathogenic	0.9945	pathogenic	-1.371	Destabilizing	0.999	D	0.892	deleterious	None	None	None	None	N
L/Q	0.9685	likely_pathogenic	0.9674	pathogenic	-2.369	Highly Destabilizing	0.999	D	0.885	deleterious	None	None	None	None	N
L/R	0.9735	likely_pathogenic	0.9724	pathogenic	-2.068	Highly Destabilizing	0.998	D	0.882	deleterious	None	None	None	None	N
L/S	0.9752	likely_pathogenic	0.9723	pathogenic	-3.309	Highly Destabilizing	0.997	D	0.845	deleterious	D	0.55104741	None	None	N
L/T	0.8612	likely_pathogenic	0.853	pathogenic	-2.826	Highly Destabilizing	0.995	D	0.802	deleterious	None	None	None	None	N
L/V	0.1359	likely_benign	0.1358	benign	-1.371	Destabilizing	0.117	N	0.452	neutral	N	0.516191571	None	None	N
L/W	0.9463	likely_pathogenic	0.9262	pathogenic	-2.053	Highly Destabilizing	1.0	D	0.838	deleterious	D	0.562403715	None	None	N
L/Y	0.9485	likely_pathogenic	0.9426	pathogenic	-1.778	Destabilizing	0.998	D	0.821	deleterious	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.