TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24551	73876;73877;73878	chr2:178572481;178572480;178572479	chr2:179437208;179437207;179437206
N2AB	22910	68953;68954;68955	chr2:178572481;178572480;178572479	chr2:179437208;179437207;179437206
N2A	21983	66172;66173;66174	chr2:178572481;178572480;178572479	chr2:179437208;179437207;179437206
N2B	15486	46681;46682;46683	chr2:178572481;178572480;178572479	chr2:179437208;179437207;179437206
Novex-1	15611	47056;47057;47058	chr2:178572481;178572480;178572479	chr2:179437208;179437207;179437206
Novex-2	15678	47257;47258;47259	chr2:178572481;178572480;178572479	chr2:179437208;179437207;179437206
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-66
• Domain position: 33
• Structural Position: 35
• Q(SASA): 0.1135
• Predicted PPI site: I

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
I/V	rs879246805	-1.647	0.05	N	0.257	0.098	None	gnomAD-2.1.1	1.79E-05	None	None	None	None	I	None	2.06765E-04	0	None	0	0	None	0	None	0	0	0
I/V	rs879246805	-1.647	0.05	N	0.257	0.098	None	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	7.24E-05	0	0	0	0	None	0	0	0	0	0
I/V	rs879246805	-1.647	0.05	N	0.257	0.098	None	gnomAD-4.0.0	8.97714E-06	None	None	None	None	I	None	1.01588E-04	0	None	0	0	None	0	0	0	1.34084E-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
I/A	0.9844	likely_pathogenic	0.9628	pathogenic	-2.554	Highly Destabilizing	0.997	D	0.692	prob.neutral	None	None	None	None	I
I/C	0.9812	likely_pathogenic	0.9593	pathogenic	-1.558	Destabilizing	1.0	D	0.729	prob.delet.	None	None	None	None	I
I/D	0.9993	likely_pathogenic	0.9978	pathogenic	-2.65	Highly Destabilizing	1.0	D	0.838	deleterious	None	None	None	None	I
I/E	0.9965	likely_pathogenic	0.9917	pathogenic	-2.547	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	I
I/F	0.9605	likely_pathogenic	0.9102	pathogenic	-1.771	Destabilizing	0.999	D	0.733	prob.delet.	D	0.541488989	None	None	I
I/G	0.997	likely_pathogenic	0.9902	pathogenic	-2.993	Highly Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	I
I/H	0.9984	likely_pathogenic	0.9952	pathogenic	-2.327	Highly Destabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
I/K	0.995	likely_pathogenic	0.9888	pathogenic	-1.956	Destabilizing	0.995	D	0.839	deleterious	None	None	None	None	I
I/L	0.5459	ambiguous	0.3888	ambiguous	-1.33	Destabilizing	0.388	N	0.459	neutral	N	0.488808839	None	None	I
I/M	0.6645	likely_pathogenic	0.4879	ambiguous	-0.911	Destabilizing	0.995	D	0.697	prob.neutral	D	0.537440519	None	None	I
I/N	0.9785	likely_pathogenic	0.9468	pathogenic	-1.956	Destabilizing	1.0	D	0.843	deleterious	D	0.545037842	None	None	I
I/P	0.9728	likely_pathogenic	0.9251	pathogenic	-1.715	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
I/Q	0.9957	likely_pathogenic	0.9889	pathogenic	-2.031	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	I
I/R	0.9941	likely_pathogenic	0.986	pathogenic	-1.365	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	I
I/S	0.9872	likely_pathogenic	0.9676	pathogenic	-2.584	Highly Destabilizing	0.999	D	0.805	deleterious	D	0.537694008	None	None	I
I/T	0.9674	likely_pathogenic	0.9364	pathogenic	-2.361	Highly Destabilizing	0.986	D	0.795	deleterious	N	0.511195962	None	None	I
I/V	0.1174	likely_benign	0.1121	benign	-1.715	Destabilizing	0.05	N	0.257	neutral	N	0.458686711	None	None	I
I/W	0.999	likely_pathogenic	0.9962	pathogenic	-2.057	Highly Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
I/Y	0.9934	likely_pathogenic	0.9823	pathogenic	-1.845	Destabilizing	0.997	D	0.765	deleterious	None	None	None	None	I

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.