TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29277	88054;88055;88056	chr2:178557433;178557432;178557431	chr2:179422160;179422159;179422158
N2AB	27636	83131;83132;83133	chr2:178557433;178557432;178557431	chr2:179422160;179422159;179422158
N2A	26709	80350;80351;80352	chr2:178557433;178557432;178557431	chr2:179422160;179422159;179422158
N2B	20212	60859;60860;60861	chr2:178557433;178557432;178557431	chr2:179422160;179422159;179422158
Novex-1	20337	61234;61235;61236	chr2:178557433;178557432;178557431	chr2:179422160;179422159;179422158
Novex-2	20404	61435;61436;61437	chr2:178557433;178557432;178557431	chr2:179422160;179422159;179422158
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: Fn3-101
• Domain position: 41
• Structural Position: 43
• Q(SASA): 0.0954
• 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	N	0.753	0.483	0.202086224978	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.66327E-05

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	0.9899	likely_pathogenic	0.9928	pathogenic	-1.532	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
K/C	0.9812	likely_pathogenic	0.9894	pathogenic	-1.643	Destabilizing	1.0	D	0.893	deleterious	None	None	None	None	N
K/D	0.999	likely_pathogenic	0.9993	pathogenic	-2.045	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
K/E	0.9898	likely_pathogenic	0.9933	pathogenic	-1.77	Destabilizing	0.999	D	0.549	neutral	N	0.506184943	None	None	N
K/F	0.9978	likely_pathogenic	0.999	pathogenic	-0.847	Destabilizing	1.0	D	0.91	deleterious	None	None	None	None	N
K/G	0.9926	likely_pathogenic	0.9947	pathogenic	-1.966	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/H	0.9195	likely_pathogenic	0.9489	pathogenic	-2.179	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
K/I	0.995	likely_pathogenic	0.9974	pathogenic	-0.303	Destabilizing	1.0	D	0.921	deleterious	N	0.512985799	None	None	N
K/L	0.9795	likely_pathogenic	0.9884	pathogenic	-0.303	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/M	0.9552	likely_pathogenic	0.9728	pathogenic	-0.681	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/N	0.9951	likely_pathogenic	0.9971	pathogenic	-1.853	Destabilizing	1.0	D	0.753	deleterious	N	0.508212859	None	None	N
K/P	0.9994	likely_pathogenic	0.9995	pathogenic	-0.693	Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
K/Q	0.8949	likely_pathogenic	0.9343	pathogenic	-1.496	Destabilizing	1.0	D	0.732	prob.delet.	N	0.479495859	None	None	N
K/R	0.1845	likely_benign	0.2177	benign	-1.331	Destabilizing	0.999	D	0.541	neutral	N	0.490446838	None	None	N
K/S	0.996	likely_pathogenic	0.9978	pathogenic	-2.311	Highly Destabilizing	0.999	D	0.609	neutral	None	None	None	None	N
K/T	0.9872	likely_pathogenic	0.9932	pathogenic	-1.804	Destabilizing	1.0	D	0.823	deleterious	N	0.504338518	None	None	N
K/V	0.9892	likely_pathogenic	0.9939	pathogenic	-0.693	Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
K/W	0.9957	likely_pathogenic	0.9984	pathogenic	-1.015	Destabilizing	1.0	D	0.887	deleterious	None	None	None	None	N
K/Y	0.988	likely_pathogenic	0.9949	pathogenic	-0.641	Destabilizing	1.0	D	0.909	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.