TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18816	56671;56672;56673	chr2:178599347;178599346;178599345	chr2:179464074;179464073;179464072
N2AB	17175	51748;51749;51750	chr2:178599347;178599346;178599345	chr2:179464074;179464073;179464072
N2A	16248	48967;48968;48969	chr2:178599347;178599346;178599345	chr2:179464074;179464073;179464072
N2B	9751	29476;29477;29478	chr2:178599347;178599346;178599345	chr2:179464074;179464073;179464072
Novex-1	9876	29851;29852;29853	chr2:178599347;178599346;178599345	chr2:179464074;179464073;179464072
Novex-2	9943	30052;30053;30054	chr2:178599347;178599346;178599345	chr2:179464074;179464073;179464072
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: Fn3-24
• Domain position: 33
• Structural Position: 34
• Q(SASA): 0.8259
• 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/R	None	None	0.928	N	0.545	0.216	0.392239652056	gnomAD-4.0.0	1.60469E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	3.04433E-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
K/A	0.3554	ambiguous	0.342	ambiguous	0.015	Stabilizing	0.895	D	0.555	neutral	None	None	None	None	I
K/C	0.7631	likely_pathogenic	0.7446	pathogenic	-0.162	Destabilizing	0.999	D	0.669	neutral	None	None	None	None	I
K/D	0.5614	ambiguous	0.5434	ambiguous	0.042	Stabilizing	0.983	D	0.569	neutral	None	None	None	None	I
K/E	0.2288	likely_benign	0.2134	benign	0.038	Stabilizing	0.928	D	0.571	neutral	N	0.444519761	None	None	I
K/F	0.8303	likely_pathogenic	0.8271	pathogenic	-0.264	Destabilizing	0.992	D	0.659	neutral	None	None	None	None	I
K/G	0.5532	ambiguous	0.5381	ambiguous	-0.163	Destabilizing	0.895	D	0.547	neutral	None	None	None	None	I
K/H	0.388	ambiguous	0.3748	ambiguous	-0.439	Destabilizing	0.998	D	0.622	neutral	None	None	None	None	I
K/I	0.4179	ambiguous	0.3979	ambiguous	0.4	Stabilizing	0.992	D	0.671	neutral	None	None	None	None	I
K/L	0.4293	ambiguous	0.4162	ambiguous	0.4	Stabilizing	0.983	D	0.539	neutral	None	None	None	None	I
K/M	0.3251	likely_benign	0.3031	benign	0.237	Stabilizing	0.999	D	0.621	neutral	N	0.468534855	None	None	I
K/N	0.4676	ambiguous	0.4532	ambiguous	0.278	Stabilizing	0.957	D	0.613	neutral	N	0.516076002	None	None	I
K/P	0.4843	ambiguous	0.4709	ambiguous	0.299	Stabilizing	0.992	D	0.638	neutral	None	None	None	None	I
K/Q	0.1835	likely_benign	0.1745	benign	0.091	Stabilizing	0.978	D	0.661	neutral	N	0.509534032	None	None	I
K/R	0.0918	likely_benign	0.0915	benign	0.024	Stabilizing	0.928	D	0.545	neutral	N	0.488409398	None	None	I
K/S	0.4676	ambiguous	0.4612	ambiguous	-0.194	Destabilizing	0.185	N	0.363	neutral	None	None	None	None	I
K/T	0.2351	likely_benign	0.2325	benign	-0.057	Destabilizing	0.865	D	0.565	neutral	D	0.523367333	None	None	I
K/V	0.3499	ambiguous	0.3384	benign	0.299	Stabilizing	0.983	D	0.619	neutral	None	None	None	None	I
K/W	0.844	likely_pathogenic	0.8399	pathogenic	-0.295	Destabilizing	0.999	D	0.719	prob.delet.	None	None	None	None	I
K/Y	0.7264	likely_pathogenic	0.7092	pathogenic	0.07	Stabilizing	0.997	D	0.658	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.