TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15308	46147;46148;46149	chr2:178620599;178620598;178620597	chr2:179485326;179485325;179485324
N2AB	13667	41224;41225;41226	chr2:178620599;178620598;178620597	chr2:179485326;179485325;179485324
N2A	12740	38443;38444;38445	chr2:178620599;178620598;178620597	chr2:179485326;179485325;179485324
N2B	6243	18952;18953;18954	chr2:178620599;178620598;178620597	chr2:179485326;179485325;179485324
Novex-1	6368	19327;19328;19329	chr2:178620599;178620598;178620597	chr2:179485326;179485325;179485324
Novex-2	6435	19528;19529;19530	chr2:178620599;178620598;178620597	chr2:179485326;179485325;179485324
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-105
• Domain position: 7
• Structural Position: 8
• Q(SASA): 0.1945
• 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/P	None	None	0.1	N	0.533	0.16	0.479744053436	gnomAD-4.0.0	1.59934E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	3.04136E-05
L/V	None	None	0.76	D	0.505	0.241	0.468917363747	gnomAD-4.0.0	1.60035E-06	None	None	None	None	N	None	0	0	None	0	2.79189E-05	None	0	0	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
L/A	0.8517	likely_pathogenic	0.7817	pathogenic	-2.169	Highly Destabilizing	0.953	D	0.58	neutral	None	None	None	None	N
L/C	0.905	likely_pathogenic	0.8822	pathogenic	-1.288	Destabilizing	0.999	D	0.762	deleterious	None	None	None	None	N
L/D	0.9986	likely_pathogenic	0.9967	pathogenic	-2.351	Highly Destabilizing	0.993	D	0.831	deleterious	None	None	None	None	N
L/E	0.9887	likely_pathogenic	0.9766	pathogenic	-2.114	Highly Destabilizing	0.993	D	0.827	deleterious	None	None	None	None	N
L/F	0.8993	likely_pathogenic	0.7701	pathogenic	-1.181	Destabilizing	0.982	D	0.67	neutral	D	0.61185936	None	None	N
L/G	0.9837	likely_pathogenic	0.9699	pathogenic	-2.713	Highly Destabilizing	0.993	D	0.824	deleterious	None	None	None	None	N
L/H	0.9923	likely_pathogenic	0.9769	pathogenic	-2.294	Highly Destabilizing	0.999	D	0.802	deleterious	D	0.615157898	None	None	N
L/I	0.2441	likely_benign	0.1762	benign	-0.601	Destabilizing	0.1	N	0.341	neutral	N	0.46279451	None	None	N
L/K	0.9884	likely_pathogenic	0.976	pathogenic	-1.484	Destabilizing	0.993	D	0.795	deleterious	None	None	None	None	N
L/M	0.4091	ambiguous	0.3374	benign	-0.588	Destabilizing	0.986	D	0.665	neutral	None	None	None	None	N
L/N	0.9905	likely_pathogenic	0.9792	pathogenic	-1.811	Destabilizing	0.998	D	0.84	deleterious	None	None	None	None	N
L/P	0.7304	likely_pathogenic	0.6137	pathogenic	-1.105	Destabilizing	0.1	N	0.533	neutral	N	0.449525206	None	None	N
L/Q	0.9715	likely_pathogenic	0.9318	pathogenic	-1.631	Destabilizing	0.998	D	0.801	deleterious	None	None	None	None	N
L/R	0.983	likely_pathogenic	0.9595	pathogenic	-1.362	Destabilizing	0.997	D	0.802	deleterious	D	0.612586862	None	None	N
L/S	0.9835	likely_pathogenic	0.9523	pathogenic	-2.485	Highly Destabilizing	0.993	D	0.758	deleterious	None	None	None	None	N
L/T	0.9224	likely_pathogenic	0.8596	pathogenic	-2.106	Highly Destabilizing	0.986	D	0.728	prob.delet.	None	None	None	None	N
L/V	0.2826	likely_benign	0.2158	benign	-1.105	Destabilizing	0.76	D	0.505	neutral	D	0.57137898	None	None	N
L/W	0.9901	likely_pathogenic	0.9625	pathogenic	-1.61	Destabilizing	0.999	D	0.75	deleterious	None	None	None	None	N
L/Y	0.994	likely_pathogenic	0.9825	pathogenic	-1.272	Destabilizing	0.998	D	0.79	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.