TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14643	44152;44153;44154	chr2:178631121;178631120;178631119	chr2:179495848;179495847;179495846
N2AB	13002	39229;39230;39231	chr2:178631121;178631120;178631119	chr2:179495848;179495847;179495846
N2A	12075	36448;36449;36450	chr2:178631121;178631120;178631119	chr2:179495848;179495847;179495846
N2B	5578	16957;16958;16959	chr2:178631121;178631120;178631119	chr2:179495848;179495847;179495846
Novex-1	5703	17332;17333;17334	chr2:178631121;178631120;178631119	chr2:179495848;179495847;179495846
Novex-2	5770	17533;17534;17535	chr2:178631121;178631120;178631119	chr2:179495848;179495847;179495846
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-97
• Domain position: 58
• Structural Position: 139
• Q(SASA): 0.155
• 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
I/N	None	None	0.896	N	0.677	0.271	0.762871968251	gnomAD-4.0.0	2.05317E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69878E-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
I/A	0.5122	ambiguous	0.5637	ambiguous	-2.845	Highly Destabilizing	0.002	N	0.391	neutral	None	None	None	None	N
I/C	0.7276	likely_pathogenic	0.7697	pathogenic	-1.958	Destabilizing	0.972	D	0.632	neutral	None	None	None	None	N
I/D	0.8412	likely_pathogenic	0.8672	pathogenic	-3.161	Highly Destabilizing	0.92	D	0.689	prob.neutral	None	None	None	None	N
I/E	0.6644	likely_pathogenic	0.7024	pathogenic	-2.987	Highly Destabilizing	0.617	D	0.677	prob.neutral	None	None	None	None	N
I/F	0.1528	likely_benign	0.1771	benign	-1.742	Destabilizing	0.81	D	0.667	neutral	D	0.549872353	None	None	N
I/G	0.8069	likely_pathogenic	0.8457	pathogenic	-3.326	Highly Destabilizing	0.447	N	0.671	neutral	None	None	None	None	N
I/H	0.4455	ambiguous	0.5088	ambiguous	-2.648	Highly Destabilizing	0.992	D	0.646	neutral	None	None	None	None	N
I/K	0.4301	ambiguous	0.5141	ambiguous	-2.319	Highly Destabilizing	0.617	D	0.679	prob.neutral	None	None	None	None	N
I/L	0.1276	likely_benign	0.1417	benign	-1.457	Destabilizing	0.099	N	0.411	neutral	N	0.493920515	None	None	N
I/M	0.1456	likely_benign	0.1575	benign	-1.259	Destabilizing	0.81	D	0.673	neutral	D	0.55891321	None	None	N
I/N	0.3859	ambiguous	0.435	ambiguous	-2.518	Highly Destabilizing	0.896	D	0.677	prob.neutral	N	0.513409637	None	None	N
I/P	0.9553	likely_pathogenic	0.971	pathogenic	-1.902	Destabilizing	0.92	D	0.68	prob.neutral	None	None	None	None	N
I/Q	0.4883	ambiguous	0.5408	ambiguous	-2.475	Highly Destabilizing	0.92	D	0.671	neutral	None	None	None	None	N
I/R	0.3112	likely_benign	0.3889	ambiguous	-1.804	Destabilizing	0.92	D	0.672	neutral	None	None	None	None	N
I/S	0.3982	ambiguous	0.4411	ambiguous	-3.162	Highly Destabilizing	0.379	N	0.659	neutral	N	0.507929336	None	None	N
I/T	0.2716	likely_benign	0.3153	benign	-2.87	Highly Destabilizing	0.007	N	0.386	neutral	N	0.456081337	None	None	N
I/V	0.0959	likely_benign	0.099	benign	-1.902	Destabilizing	0.002	N	0.177	neutral	N	0.468000746	None	None	N
I/W	0.7591	likely_pathogenic	0.8034	pathogenic	-2.114	Highly Destabilizing	0.992	D	0.668	neutral	None	None	None	None	N
I/Y	0.4415	ambiguous	0.5032	ambiguous	-1.914	Destabilizing	0.92	D	0.653	neutral	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.