TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22471	67636;67637;67638	chr2:178579786;178579785;178579784	chr2:179444513;179444512;179444511
N2AB	20830	62713;62714;62715	chr2:178579786;178579785;178579784	chr2:179444513;179444512;179444511
N2A	19903	59932;59933;59934	chr2:178579786;178579785;178579784	chr2:179444513;179444512;179444511
N2B	13406	40441;40442;40443	chr2:178579786;178579785;178579784	chr2:179444513;179444512;179444511
Novex-1	13531	40816;40817;40818	chr2:178579786;178579785;178579784	chr2:179444513;179444512;179444511
Novex-2	13598	41017;41018;41019	chr2:178579786;178579785;178579784	chr2:179444513;179444512;179444511
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-51
• Domain position: 21
• Structural Position: 23
• Q(SASA): 0.0764
• 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
G/S	None	None	None	N	0.228	0.128	0.107399877778	gnomAD-4.0.0	1.59234E-06	None	None	None	None	N	None	0	0	None	0	2.77886E-05	None	0	0	0	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
G/A	0.0677	likely_benign	0.0675	benign	-0.602	Destabilizing	None	N	0.207	neutral	N	0.412428772	None	None	N
G/C	0.1302	likely_benign	0.1197	benign	-0.884	Destabilizing	0.78	D	0.645	neutral	N	0.466705974	None	None	N
G/D	0.2822	likely_benign	0.2702	benign	-2.338	Highly Destabilizing	0.117	N	0.669	neutral	N	0.472207794	None	None	N
G/E	0.2079	likely_benign	0.2051	benign	-2.127	Highly Destabilizing	0.081	N	0.679	prob.neutral	None	None	None	None	N
G/F	0.3525	ambiguous	0.3603	ambiguous	-0.469	Destabilizing	0.555	D	0.691	prob.neutral	None	None	None	None	N
G/H	0.3476	ambiguous	0.3194	benign	-2.005	Highly Destabilizing	0.824	D	0.617	neutral	None	None	None	None	N
G/I	0.1343	likely_benign	0.1331	benign	0.597	Stabilizing	0.081	N	0.68	prob.neutral	None	None	None	None	N
G/K	0.5359	ambiguous	0.5125	ambiguous	-1.124	Destabilizing	0.081	N	0.676	prob.neutral	None	None	None	None	N
G/L	0.2092	likely_benign	0.2049	benign	0.597	Stabilizing	0.081	N	0.634	neutral	None	None	None	None	N
G/M	0.2588	likely_benign	0.2589	benign	0.238	Stabilizing	0.824	D	0.648	neutral	None	None	None	None	N
G/N	0.2673	likely_benign	0.2534	benign	-1.449	Destabilizing	0.081	N	0.643	neutral	None	None	None	None	N
G/P	0.9524	likely_pathogenic	0.9584	pathogenic	0.242	Stabilizing	0.38	N	0.663	neutral	None	None	None	None	N
G/Q	0.3	likely_benign	0.296	benign	-1.193	Destabilizing	0.38	N	0.676	prob.neutral	None	None	None	None	N
G/R	0.354	ambiguous	0.3527	ambiguous	-1.366	Destabilizing	0.317	N	0.656	neutral	N	0.43778579	None	None	N
G/S	0.0708	likely_benign	0.0679	benign	-1.719	Destabilizing	None	N	0.228	neutral	N	0.361071658	None	None	N
G/T	0.0796	likely_benign	0.0779	benign	-1.393	Destabilizing	0.002	N	0.463	neutral	None	None	None	None	N
G/V	0.1062	likely_benign	0.1065	benign	0.242	Stabilizing	None	N	0.635	neutral	N	0.455758262	None	None	N
G/W	0.3372	likely_benign	0.3347	benign	-1.454	Destabilizing	0.935	D	0.647	neutral	None	None	None	None	N
G/Y	0.321	likely_benign	0.3107	benign	-0.765	Destabilizing	0.555	D	0.659	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.