TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26883	80872;80873;80874	chr2:178565485;178565484;178565483	chr2:179430212;179430211;179430210
N2AB	25242	75949;75950;75951	chr2:178565485;178565484;178565483	chr2:179430212;179430211;179430210
N2A	24315	73168;73169;73170	chr2:178565485;178565484;178565483	chr2:179430212;179430211;179430210
N2B	17818	53677;53678;53679	chr2:178565485;178565484;178565483	chr2:179430212;179430211;179430210
Novex-1	17943	54052;54053;54054	chr2:178565485;178565484;178565483	chr2:179430212;179430211;179430210
Novex-2	18010	54253;54254;54255	chr2:178565485;178565484;178565483	chr2:179430212;179430211;179430210
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-139
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.571
• 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
K/N	None	None	0.901	N	0.486	0.145	0.12205267543	gnomAD-4.0.0	1.59254E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.8604E-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
K/A	0.4255	ambiguous	0.4473	ambiguous	-0.084	Destabilizing	0.633	D	0.499	neutral	None	None	None	None	I
K/C	0.6606	likely_pathogenic	0.6816	pathogenic	-0.357	Destabilizing	0.996	D	0.641	neutral	None	None	None	None	I
K/D	0.6073	likely_pathogenic	0.6353	pathogenic	0.107	Stabilizing	0.923	D	0.477	neutral	None	None	None	None	I
K/E	0.2635	likely_benign	0.2801	benign	0.176	Stabilizing	0.565	D	0.541	neutral	N	0.434139691	None	None	I
K/F	0.7376	likely_pathogenic	0.7421	pathogenic	-0.014	Destabilizing	0.923	D	0.629	neutral	None	None	None	None	I
K/G	0.5851	likely_pathogenic	0.601	pathogenic	-0.363	Destabilizing	0.923	D	0.485	neutral	None	None	None	None	I
K/H	0.2455	likely_benign	0.2422	benign	-0.566	Destabilizing	0.989	D	0.531	neutral	None	None	None	None	I
K/I	0.3404	ambiguous	0.3647	ambiguous	0.596	Stabilizing	0.858	D	0.624	neutral	None	None	None	None	I
K/L	0.3615	ambiguous	0.375	ambiguous	0.596	Stabilizing	0.372	N	0.485	neutral	None	None	None	None	I
K/M	0.2755	likely_benign	0.2934	benign	0.152	Stabilizing	0.156	N	0.399	neutral	N	0.49024369	None	None	I
K/N	0.4398	ambiguous	0.4542	ambiguous	-0.042	Destabilizing	0.901	D	0.486	neutral	N	0.460614216	None	None	I
K/P	0.742	likely_pathogenic	0.7462	pathogenic	0.399	Stabilizing	0.961	D	0.525	neutral	None	None	None	None	I
K/Q	0.1353	likely_benign	0.1327	benign	-0.08	Destabilizing	0.075	N	0.271	neutral	N	0.45486168	None	None	I
K/R	0.0859	likely_benign	0.0801	benign	-0.216	Destabilizing	0.565	D	0.509	neutral	N	0.415727288	None	None	I
K/S	0.4436	ambiguous	0.4568	ambiguous	-0.544	Destabilizing	0.775	D	0.505	neutral	None	None	None	None	I
K/T	0.1999	likely_benign	0.2163	benign	-0.294	Destabilizing	0.901	D	0.474	neutral	N	0.449567716	None	None	I
K/V	0.3235	likely_benign	0.3374	benign	0.399	Stabilizing	0.633	D	0.479	neutral	None	None	None	None	I
K/W	0.7331	likely_pathogenic	0.7434	pathogenic	-0.027	Destabilizing	0.996	D	0.656	neutral	None	None	None	None	I
K/Y	0.5673	likely_pathogenic	0.5865	pathogenic	0.302	Stabilizing	0.961	D	0.582	neutral	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.