TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30706	92341;92342;92343	chr2:178549606;178549605;178549604	chr2:179414333;179414332;179414331
N2AB	29065	87418;87419;87420	chr2:178549606;178549605;178549604	chr2:179414333;179414332;179414331
N2A	28138	84637;84638;84639	chr2:178549606;178549605;178549604	chr2:179414333;179414332;179414331
N2B	21641	65146;65147;65148	chr2:178549606;178549605;178549604	chr2:179414333;179414332;179414331
Novex-1	21766	65521;65522;65523	chr2:178549606;178549605;178549604	chr2:179414333;179414332;179414331
Novex-2	21833	65722;65723;65724	chr2:178549606;178549605;178549604	chr2:179414333;179414332;179414331
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: Fn3-111
• Domain position: 88
• Structural Position: 121
• Q(SASA): 0.1151
• 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/R	rs779567470	-1.065	0.999	N	0.855	0.622	0.79003172286	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	9E-06	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	0.2278	likely_benign	0.2616	benign	-2.047	Highly Destabilizing	0.998	D	0.798	deleterious	None	None	None	None	N
L/C	0.464	ambiguous	0.4756	ambiguous	-1.44	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
L/D	0.8718	likely_pathogenic	0.8916	pathogenic	-1.39	Destabilizing	1.0	D	0.895	deleterious	None	None	None	None	N
L/E	0.489	ambiguous	0.5388	ambiguous	-1.294	Destabilizing	0.999	D	0.849	deleterious	None	None	None	None	N
L/F	0.3079	likely_benign	0.3272	benign	-1.214	Destabilizing	0.999	D	0.743	deleterious	D	0.527444247	None	None	N
L/G	0.6764	likely_pathogenic	0.6927	pathogenic	-2.472	Highly Destabilizing	0.999	D	0.817	deleterious	None	None	None	None	N
L/H	0.4504	ambiguous	0.493	ambiguous	-1.65	Destabilizing	1.0	D	0.869	deleterious	D	0.539472116	None	None	N
L/I	0.0973	likely_benign	0.1175	benign	-0.898	Destabilizing	0.997	D	0.713	prob.delet.	N	0.487499528	None	None	N
L/K	0.4789	ambiguous	0.5143	ambiguous	-1.394	Destabilizing	0.999	D	0.809	deleterious	None	None	None	None	N
L/M	0.1173	likely_benign	0.1276	benign	-0.869	Destabilizing	0.999	D	0.755	deleterious	None	None	None	None	N
L/N	0.6029	likely_pathogenic	0.6465	pathogenic	-1.346	Destabilizing	1.0	D	0.901	deleterious	None	None	None	None	N
L/P	0.975	likely_pathogenic	0.9748	pathogenic	-1.253	Destabilizing	1.0	D	0.897	deleterious	D	0.538711647	None	None	N
L/Q	0.2029	likely_benign	0.2265	benign	-1.404	Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
L/R	0.3607	ambiguous	0.4054	ambiguous	-0.943	Destabilizing	0.999	D	0.855	deleterious	N	0.520100413	None	None	N
L/S	0.3467	ambiguous	0.3985	ambiguous	-2.11	Highly Destabilizing	0.999	D	0.772	deleterious	None	None	None	None	N
L/T	0.203	likely_benign	0.2123	benign	-1.882	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
L/V	0.0868	likely_benign	0.1024	benign	-1.253	Destabilizing	0.997	D	0.694	prob.delet.	N	0.482877945	None	None	N
L/W	0.6197	likely_pathogenic	0.6362	pathogenic	-1.335	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
L/Y	0.6192	likely_pathogenic	0.6285	pathogenic	-1.104	Destabilizing	0.999	D	0.746	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.