TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23156	69691;69692;69693	chr2:178576778;178576777;178576776	chr2:179441505;179441504;179441503
N2AB	21515	64768;64769;64770	chr2:178576778;178576777;178576776	chr2:179441505;179441504;179441503
N2A	20588	61987;61988;61989	chr2:178576778;178576777;178576776	chr2:179441505;179441504;179441503
N2B	14091	42496;42497;42498	chr2:178576778;178576777;178576776	chr2:179441505;179441504;179441503
Novex-1	14216	42871;42872;42873	chr2:178576778;178576777;178576776	chr2:179441505;179441504;179441503
Novex-2	14283	43072;43073;43074	chr2:178576778;178576777;178576776	chr2:179441505;179441504;179441503
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-56
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.0951
• 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
A/V	rs748627799	-0.097	0.002	N	0.26	0.082	0.171388866994	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	6.46E-05	0	None	0	0	None	0	None	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
A/C	0.5265	ambiguous	0.5311	ambiguous	-2.15	Highly Destabilizing	0.991	D	0.685	prob.neutral	None	None	None	None	N
A/D	0.9927	likely_pathogenic	0.9943	pathogenic	-2.697	Highly Destabilizing	0.989	D	0.793	deleterious	N	0.496421572	None	None	N
A/E	0.9835	likely_pathogenic	0.9859	pathogenic	-2.524	Highly Destabilizing	0.915	D	0.783	deleterious	None	None	None	None	N
A/F	0.8824	likely_pathogenic	0.8995	pathogenic	-1.124	Destabilizing	0.949	D	0.795	deleterious	None	None	None	None	N
A/G	0.3672	ambiguous	0.39	ambiguous	-1.858	Destabilizing	0.891	D	0.657	neutral	N	0.473544377	None	None	N
A/H	0.9912	likely_pathogenic	0.9931	pathogenic	-2.109	Highly Destabilizing	0.998	D	0.767	deleterious	None	None	None	None	N
A/I	0.3531	ambiguous	0.3321	benign	-0.201	Destabilizing	0.029	N	0.506	neutral	None	None	None	None	N
A/K	0.9949	likely_pathogenic	0.9959	pathogenic	-1.621	Destabilizing	0.915	D	0.796	deleterious	None	None	None	None	N
A/L	0.3884	ambiguous	0.4018	ambiguous	-0.201	Destabilizing	0.325	N	0.572	neutral	None	None	None	None	N
A/M	0.468	ambiguous	0.501	ambiguous	-0.668	Destabilizing	0.974	D	0.808	deleterious	None	None	None	None	N
A/N	0.9749	likely_pathogenic	0.9798	pathogenic	-1.969	Destabilizing	0.991	D	0.81	deleterious	None	None	None	None	N
A/P	0.9922	likely_pathogenic	0.9918	pathogenic	-0.56	Destabilizing	0.989	D	0.814	deleterious	N	0.496421572	None	None	N
A/Q	0.9706	likely_pathogenic	0.9744	pathogenic	-1.842	Destabilizing	0.991	D	0.824	deleterious	None	None	None	None	N
A/R	0.9866	likely_pathogenic	0.9881	pathogenic	-1.587	Destabilizing	0.974	D	0.819	deleterious	None	None	None	None	N
A/S	0.3405	ambiguous	0.3529	ambiguous	-2.434	Highly Destabilizing	0.891	D	0.633	neutral	N	0.464074176	None	None	N
A/T	0.2579	likely_benign	0.2925	benign	-2.125	Highly Destabilizing	0.801	D	0.621	neutral	N	0.466454033	None	None	N
A/V	0.1326	likely_benign	0.1216	benign	-0.56	Destabilizing	0.002	N	0.26	neutral	N	0.375459534	None	None	N
A/W	0.994	likely_pathogenic	0.9953	pathogenic	-1.735	Destabilizing	0.998	D	0.778	deleterious	None	None	None	None	N
A/Y	0.9751	likely_pathogenic	0.9793	pathogenic	-1.25	Destabilizing	0.974	D	0.811	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.