TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25158	75697;75698;75699	chr2:178570660;178570659;178570658	chr2:179435387;179435386;179435385
N2AB	23517	70774;70775;70776	chr2:178570660;178570659;178570658	chr2:179435387;179435386;179435385
N2A	22590	67993;67994;67995	chr2:178570660;178570659;178570658	chr2:179435387;179435386;179435385
N2B	16093	48502;48503;48504	chr2:178570660;178570659;178570658	chr2:179435387;179435386;179435385
Novex-1	16218	48877;48878;48879	chr2:178570660;178570659;178570658	chr2:179435387;179435386;179435385
Novex-2	16285	49078;49079;49080	chr2:178570660;178570659;178570658	chr2:179435387;179435386;179435385
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-134
• Domain position: 48
• Structural Position: 121
• Q(SASA): 0.166
• 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/S	None	None	0.967	N	0.679	0.525	0.783148497913	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	7.32654E-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
L/A	0.2688	likely_benign	0.2882	benign	-2.299	Highly Destabilizing	0.845	D	0.512	neutral	None	None	None	None	N
L/C	0.3642	ambiguous	0.3833	ambiguous	-1.75	Destabilizing	0.999	D	0.67	neutral	None	None	None	None	N
L/D	0.8468	likely_pathogenic	0.8712	pathogenic	-1.885	Destabilizing	0.996	D	0.778	deleterious	None	None	None	None	N
L/E	0.5007	ambiguous	0.524	ambiguous	-1.785	Destabilizing	0.987	D	0.769	deleterious	None	None	None	None	N
L/F	0.151	likely_benign	0.1548	benign	-1.556	Destabilizing	0.967	D	0.602	neutral	N	0.465141041	None	None	N
L/G	0.5812	likely_pathogenic	0.6237	pathogenic	-2.74	Highly Destabilizing	0.987	D	0.757	deleterious	None	None	None	None	N
L/H	0.2721	likely_benign	0.2917	benign	-1.991	Destabilizing	0.999	D	0.748	deleterious	None	None	None	None	N
L/I	0.0936	likely_benign	0.0938	benign	-1.093	Destabilizing	0.099	N	0.405	neutral	N	0.41648309	None	None	N
L/K	0.3218	likely_benign	0.345	ambiguous	-1.644	Destabilizing	0.975	D	0.707	prob.neutral	None	None	None	None	N
L/M	0.087	likely_benign	0.087	benign	-0.988	Destabilizing	0.693	D	0.47	neutral	None	None	None	None	N
L/N	0.5085	ambiguous	0.5552	ambiguous	-1.636	Destabilizing	0.996	D	0.777	deleterious	None	None	None	None	N
L/P	0.9297	likely_pathogenic	0.9487	pathogenic	-1.469	Destabilizing	0.996	D	0.778	deleterious	None	None	None	None	N
L/Q	0.1957	likely_benign	0.2054	benign	-1.701	Destabilizing	0.987	D	0.729	prob.delet.	None	None	None	None	N
L/R	0.2421	likely_benign	0.2599	benign	-1.156	Destabilizing	0.987	D	0.731	prob.delet.	None	None	None	None	N
L/S	0.3568	ambiguous	0.388	ambiguous	-2.399	Highly Destabilizing	0.967	D	0.679	prob.neutral	N	0.517418088	None	None	N
L/T	0.1879	likely_benign	0.1957	benign	-2.161	Highly Destabilizing	0.975	D	0.642	neutral	None	None	None	None	N
L/V	0.0893	likely_benign	0.0888	benign	-1.469	Destabilizing	0.025	N	0.387	neutral	N	0.413096068	None	None	N
L/W	0.254	likely_benign	0.2578	benign	-1.71	Destabilizing	0.999	D	0.683	prob.neutral	None	None	None	None	N
L/Y	0.3444	ambiguous	0.3586	ambiguous	-1.48	Destabilizing	0.987	D	0.712	prob.delet.	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.