TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15481	46666;46667;46668	chr2:178619876;178619875;178619874	chr2:179484603;179484602;179484601
N2AB	13840	41743;41744;41745	chr2:178619876;178619875;178619874	chr2:179484603;179484602;179484601
N2A	12913	38962;38963;38964	chr2:178619876;178619875;178619874	chr2:179484603;179484602;179484601
N2B	6416	19471;19472;19473	chr2:178619876;178619875;178619874	chr2:179484603;179484602;179484601
Novex-1	6541	19846;19847;19848	chr2:178619876;178619875;178619874	chr2:179484603;179484602;179484601
Novex-2	6608	20047;20048;20049	chr2:178619876;178619875;178619874	chr2:179484603;179484602;179484601
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-107
• Domain position: 2
• Structural Position: 2
• Q(SASA): 0.3928
• 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
E/Q	None	None	1.0	D	0.591	0.421	0.461323234107	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	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
E/A	0.4961	ambiguous	0.4694	ambiguous	-0.356	Destabilizing	0.999	D	0.568	neutral	D	0.590727911	None	None	N
E/C	0.9732	likely_pathogenic	0.9777	pathogenic	-0.385	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
E/D	0.3394	likely_benign	0.3383	benign	-0.479	Destabilizing	0.999	D	0.406	neutral	D	0.543686399	None	None	N
E/F	0.9638	likely_pathogenic	0.9702	pathogenic	0.068	Stabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
E/G	0.6515	likely_pathogenic	0.5988	pathogenic	-0.597	Destabilizing	1.0	D	0.633	neutral	D	0.547045194	None	None	N
E/H	0.8044	likely_pathogenic	0.8228	pathogenic	0.461	Stabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
E/I	0.7946	likely_pathogenic	0.8234	pathogenic	0.26	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
E/K	0.5039	ambiguous	0.4936	ambiguous	0.15	Stabilizing	0.999	D	0.527	neutral	D	0.536286026	None	None	N
E/L	0.8519	likely_pathogenic	0.869	pathogenic	0.26	Stabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
E/M	0.8325	likely_pathogenic	0.8502	pathogenic	0.138	Stabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
E/N	0.5958	likely_pathogenic	0.6098	pathogenic	-0.412	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
E/P	0.9892	likely_pathogenic	0.9901	pathogenic	0.075	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	N
E/Q	0.3025	likely_benign	0.2937	benign	-0.318	Destabilizing	1.0	D	0.591	neutral	D	0.548071407	None	None	N
E/R	0.6422	likely_pathogenic	0.6423	pathogenic	0.551	Stabilizing	1.0	D	0.68	prob.neutral	None	None	None	None	N
E/S	0.5332	ambiguous	0.524	ambiguous	-0.562	Destabilizing	0.999	D	0.581	neutral	None	None	None	None	N
E/T	0.5358	ambiguous	0.5399	ambiguous	-0.351	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
E/V	0.5586	ambiguous	0.5998	pathogenic	0.075	Stabilizing	1.0	D	0.643	neutral	D	0.592405837	None	None	N
E/W	0.9896	likely_pathogenic	0.9915	pathogenic	0.286	Stabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/Y	0.9262	likely_pathogenic	0.9381	pathogenic	0.325	Stabilizing	1.0	D	0.703	prob.neutral	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.