TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21973	66142;66143;66144	chr2:178582539;178582538;178582537	chr2:179447266;179447265;179447264
N2AB	20332	61219;61220;61221	chr2:178582539;178582538;178582537	chr2:179447266;179447265;179447264
N2A	19405	58438;58439;58440	chr2:178582539;178582538;178582537	chr2:179447266;179447265;179447264
N2B	12908	38947;38948;38949	chr2:178582539;178582538;178582537	chr2:179447266;179447265;179447264
Novex-1	13033	39322;39323;39324	chr2:178582539;178582538;178582537	chr2:179447266;179447265;179447264
Novex-2	13100	39523;39524;39525	chr2:178582539;178582538;178582537	chr2:179447266;179447265;179447264
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Fn3-47
• Domain position: 18
• Structural Position: 20
• Q(SASA): 0.1071
• 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
A/V	None	None	0.012	N	0.302	0.257	0.239305524855	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	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
A/C	0.3642	ambiguous	0.3693	ambiguous	-1.323	Destabilizing	0.996	D	0.693	prob.neutral	None	None	None	None	N
A/D	0.9944	likely_pathogenic	0.9915	pathogenic	-2.672	Highly Destabilizing	0.884	D	0.798	deleterious	N	0.501807304	None	None	N
A/E	0.986	likely_pathogenic	0.9778	pathogenic	-2.409	Highly Destabilizing	0.953	D	0.826	deleterious	None	None	None	None	N
A/F	0.8241	likely_pathogenic	0.7989	pathogenic	-0.703	Destabilizing	0.953	D	0.813	deleterious	None	None	None	None	N
A/G	0.3955	ambiguous	0.3441	ambiguous	-1.766	Destabilizing	0.007	N	0.366	neutral	N	0.500539857	None	None	N
A/H	0.988	likely_pathogenic	0.9839	pathogenic	-2.328	Highly Destabilizing	0.996	D	0.765	deleterious	None	None	None	None	N
A/I	0.3695	ambiguous	0.3292	benign	0.322	Stabilizing	0.037	N	0.561	neutral	None	None	None	None	N
A/K	0.9952	likely_pathogenic	0.9917	pathogenic	-1.356	Destabilizing	0.91	D	0.827	deleterious	None	None	None	None	N
A/L	0.3772	ambiguous	0.3359	benign	0.322	Stabilizing	0.373	N	0.657	neutral	None	None	None	None	N
A/M	0.4516	ambiguous	0.3862	ambiguous	-0.018	Destabilizing	0.953	D	0.799	deleterious	None	None	None	None	N
A/N	0.9778	likely_pathogenic	0.9674	pathogenic	-1.835	Destabilizing	0.91	D	0.813	deleterious	None	None	None	None	N
A/P	0.9915	likely_pathogenic	0.9917	pathogenic	-0.145	Destabilizing	0.979	D	0.827	deleterious	N	0.501553815	None	None	N
A/Q	0.9682	likely_pathogenic	0.953	pathogenic	-1.515	Destabilizing	0.984	D	0.804	deleterious	None	None	None	None	N
A/R	0.9875	likely_pathogenic	0.9807	pathogenic	-1.593	Destabilizing	0.953	D	0.825	deleterious	None	None	None	None	N
A/S	0.3883	ambiguous	0.3551	ambiguous	-2.255	Highly Destabilizing	0.684	D	0.649	neutral	N	0.474802279	None	None	N
A/T	0.3639	ambiguous	0.299	benign	-1.844	Destabilizing	0.684	D	0.676	prob.neutral	N	0.489437041	None	None	N
A/V	0.155	likely_benign	0.1396	benign	-0.145	Destabilizing	0.012	N	0.302	neutral	N	0.38951184	None	None	N
A/W	0.9905	likely_pathogenic	0.9886	pathogenic	-1.595	Destabilizing	0.996	D	0.781	deleterious	None	None	None	None	N
A/Y	0.9577	likely_pathogenic	0.9491	pathogenic	-1.003	Destabilizing	0.984	D	0.789	deleterious	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.