TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32406	97441;97442;97443	chr2:178542540;178542539;178542538	chr2:179407267;179407266;179407265
N2AB	30765	92518;92519;92520	chr2:178542540;178542539;178542538	chr2:179407267;179407266;179407265
N2A	29838	89737;89738;89739	chr2:178542540;178542539;178542538	chr2:179407267;179407266;179407265
N2B	23341	70246;70247;70248	chr2:178542540;178542539;178542538	chr2:179407267;179407266;179407265
Novex-1	23466	70621;70622;70623	chr2:178542540;178542539;178542538	chr2:179407267;179407266;179407265
Novex-2	23533	70822;70823;70824	chr2:178542540;178542539;178542538	chr2:179407267;179407266;179407265
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-124
• Domain position: 8
• Structural Position: 8
• Q(SASA): 0.6845
• 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
P/L	rs1469824341	0.078	0.999	N	0.749	0.434	0.616575112523	gnomAD-2.1.1	4.07E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.32E-05	None	0	0	0
P/L	rs1469824341	0.078	0.999	N	0.749	0.434	0.616575112523	gnomAD-4.0.0	1.61253E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.44275E-05	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
P/A	0.2964	likely_benign	0.2204	benign	-0.426	Destabilizing	0.996	D	0.642	neutral	N	0.499121052	None	None	I
P/C	0.784	likely_pathogenic	0.6625	pathogenic	-0.77	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	I
P/D	0.6225	likely_pathogenic	0.5708	pathogenic	-0.214	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	I
P/E	0.4877	ambiguous	0.4226	ambiguous	-0.313	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
P/F	0.8351	likely_pathogenic	0.7245	pathogenic	-0.618	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
P/G	0.642	likely_pathogenic	0.558	ambiguous	-0.537	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
P/H	0.5251	ambiguous	0.4048	ambiguous	-0.024	Destabilizing	1.0	D	0.75	deleterious	D	0.529026139	None	None	I
P/I	0.6517	likely_pathogenic	0.5362	ambiguous	-0.274	Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	I
P/K	0.5555	ambiguous	0.469	ambiguous	-0.444	Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	I
P/L	0.4016	ambiguous	0.2901	benign	-0.274	Destabilizing	0.999	D	0.749	deleterious	N	0.507938781	None	None	I
P/M	0.6196	likely_pathogenic	0.4966	ambiguous	-0.541	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
P/N	0.6038	likely_pathogenic	0.5133	ambiguous	-0.269	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
P/Q	0.4492	ambiguous	0.3378	benign	-0.459	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
P/R	0.4829	ambiguous	0.3618	ambiguous	0.023	Stabilizing	0.999	D	0.791	deleterious	N	0.520125369	None	None	I
P/S	0.4293	ambiguous	0.3246	benign	-0.624	Destabilizing	0.998	D	0.752	deleterious	N	0.506869733	None	None	I
P/T	0.3337	likely_benign	0.2483	benign	-0.622	Destabilizing	0.884	D	0.344	neutral	N	0.502919713	None	None	I
P/V	0.518	ambiguous	0.408	ambiguous	-0.293	Destabilizing	0.999	D	0.717	prob.delet.	None	None	None	None	I
P/W	0.9243	likely_pathogenic	0.8674	pathogenic	-0.689	Destabilizing	1.0	D	0.773	deleterious	None	None	None	None	I
P/Y	0.8004	likely_pathogenic	0.6876	pathogenic	-0.411	Destabilizing	1.0	D	0.759	deleterious	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.