TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17639	53140;53141;53142	chr2:178607872;178607871;178607870	chr2:179472599;179472598;179472597
N2AB	15998	48217;48218;48219	chr2:178607872;178607871;178607870	chr2:179472599;179472598;179472597
N2A	15071	45436;45437;45438	chr2:178607872;178607871;178607870	chr2:179472599;179472598;179472597
N2B	8574	25945;25946;25947	chr2:178607872;178607871;178607870	chr2:179472599;179472598;179472597
Novex-1	8699	26320;26321;26322	chr2:178607872;178607871;178607870	chr2:179472599;179472598;179472597
Novex-2	8766	26521;26522;26523	chr2:178607872;178607871;178607870	chr2:179472599;179472598;179472597
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-16
• Domain position: 71
• Structural Position: 103
• Q(SASA): 0.3575
• 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
D/N	None	None	0.989	N	0.553	0.329	0.292787519742	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	1.94099E-04	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
D/A	0.2087	likely_benign	0.2137	benign	-0.395	Destabilizing	0.978	D	0.579	neutral	N	0.462049516	None	None	N
D/C	0.7134	likely_pathogenic	0.7399	pathogenic	-0.121	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
D/E	0.2456	likely_benign	0.2536	benign	-0.565	Destabilizing	0.948	D	0.447	neutral	N	0.408791034	None	None	N
D/F	0.6785	likely_pathogenic	0.6554	pathogenic	0.192	Stabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
D/G	0.3368	likely_benign	0.3454	ambiguous	-0.795	Destabilizing	0.989	D	0.532	neutral	N	0.477923045	None	None	N
D/H	0.3553	ambiguous	0.3561	ambiguous	-0.117	Destabilizing	1.0	D	0.687	prob.neutral	N	0.473686189	None	None	N
D/I	0.3939	ambiguous	0.4021	ambiguous	0.672	Stabilizing	0.999	D	0.771	deleterious	None	None	None	None	N
D/K	0.4283	ambiguous	0.4535	ambiguous	-0.203	Destabilizing	0.246	N	0.287	neutral	None	None	None	None	N
D/L	0.43	ambiguous	0.4454	ambiguous	0.672	Stabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	N
D/M	0.675	likely_pathogenic	0.6824	pathogenic	1.07	Stabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	N
D/N	0.1191	likely_benign	0.1204	benign	-0.796	Destabilizing	0.989	D	0.553	neutral	N	0.468551414	None	None	N
D/P	0.7686	likely_pathogenic	0.7884	pathogenic	0.343	Stabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
D/Q	0.3762	ambiguous	0.4018	ambiguous	-0.596	Destabilizing	0.995	D	0.599	neutral	None	None	None	None	N
D/R	0.4656	ambiguous	0.4837	ambiguous	-0.052	Destabilizing	0.99	D	0.635	neutral	None	None	None	None	N
D/S	0.166	likely_benign	0.1746	benign	-1.077	Destabilizing	0.983	D	0.482	neutral	None	None	None	None	N
D/T	0.2761	likely_benign	0.3007	benign	-0.734	Destabilizing	0.992	D	0.599	neutral	None	None	None	None	N
D/V	0.2342	likely_benign	0.2422	benign	0.343	Stabilizing	0.997	D	0.737	prob.delet.	N	0.475402815	None	None	N
D/W	0.9191	likely_pathogenic	0.9142	pathogenic	0.389	Stabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
D/Y	0.2896	likely_benign	0.2739	benign	0.463	Stabilizing	0.999	D	0.757	deleterious	N	0.489660192	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.