TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28415	85468;85469;85470	chr2:178560889;178560888;178560887	chr2:179425616;179425615;179425614
N2AB	26774	80545;80546;80547	chr2:178560889;178560888;178560887	chr2:179425616;179425615;179425614
N2A	25847	77764;77765;77766	chr2:178560889;178560888;178560887	chr2:179425616;179425615;179425614
N2B	19350	58273;58274;58275	chr2:178560889;178560888;178560887	chr2:179425616;179425615;179425614
Novex-1	19475	58648;58649;58650	chr2:178560889;178560888;178560887	chr2:179425616;179425615;179425614
Novex-2	19542	58849;58850;58851	chr2:178560889;178560888;178560887	chr2:179425616;179425615;179425614
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-143
• Domain position: 58
• Structural Position: 138
• Q(SASA): 0.0799
• 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/F	None	None	0.978	N	0.785	0.501	0.675152924593	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.8988	likely_pathogenic	0.8872	pathogenic	-2.671	Highly Destabilizing	0.944	D	0.736	prob.delet.	None	None	None	None	N
L/C	0.8368	likely_pathogenic	0.8137	pathogenic	-1.916	Destabilizing	0.999	D	0.848	deleterious	None	None	None	None	N
L/D	0.9993	likely_pathogenic	0.999	pathogenic	-3.451	Highly Destabilizing	0.997	D	0.917	deleterious	None	None	None	None	N
L/E	0.9943	likely_pathogenic	0.9924	pathogenic	-3.12	Highly Destabilizing	0.997	D	0.904	deleterious	None	None	None	None	N
L/F	0.452	ambiguous	0.4306	ambiguous	-1.618	Destabilizing	0.978	D	0.785	deleterious	N	0.517419339	None	None	N
L/G	0.9853	likely_pathogenic	0.9821	pathogenic	-3.293	Highly Destabilizing	0.992	D	0.897	deleterious	None	None	None	None	N
L/H	0.9765	likely_pathogenic	0.9678	pathogenic	-3.016	Highly Destabilizing	0.999	D	0.909	deleterious	None	None	None	None	N
L/I	0.157	likely_benign	0.1662	benign	-0.801	Destabilizing	0.039	N	0.357	neutral	N	0.494515691	None	None	N
L/K	0.9866	likely_pathogenic	0.9828	pathogenic	-2.159	Highly Destabilizing	0.992	D	0.899	deleterious	None	None	None	None	N
L/M	0.2994	likely_benign	0.2797	benign	-0.93	Destabilizing	0.983	D	0.772	deleterious	None	None	None	None	N
L/N	0.9952	likely_pathogenic	0.9935	pathogenic	-2.897	Highly Destabilizing	0.997	D	0.926	deleterious	None	None	None	None	N
L/P	0.9936	likely_pathogenic	0.991	pathogenic	-1.415	Destabilizing	0.997	D	0.926	deleterious	None	None	None	None	N
L/Q	0.9675	likely_pathogenic	0.9568	pathogenic	-2.525	Highly Destabilizing	0.999	D	0.925	deleterious	None	None	None	None	N
L/R	0.9717	likely_pathogenic	0.9632	pathogenic	-2.249	Highly Destabilizing	0.997	D	0.921	deleterious	None	None	None	None	N
L/S	0.989	likely_pathogenic	0.9851	pathogenic	-3.461	Highly Destabilizing	0.989	D	0.893	deleterious	D	0.56618915	None	None	N
L/T	0.9644	likely_pathogenic	0.9588	pathogenic	-2.957	Highly Destabilizing	0.983	D	0.833	deleterious	None	None	None	None	N
L/V	0.2114	likely_benign	0.214	benign	-1.415	Destabilizing	0.476	N	0.705	prob.neutral	N	0.509443622	None	None	N
L/W	0.9089	likely_pathogenic	0.8767	pathogenic	-2.043	Highly Destabilizing	0.999	D	0.887	deleterious	None	None	None	None	N
L/Y	0.9218	likely_pathogenic	0.9005	pathogenic	-1.796	Destabilizing	0.992	D	0.847	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.