TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21605	65038;65039;65040	chr2:178584828;178584827;178584826	chr2:179449555;179449554;179449553
N2AB	19964	60115;60116;60117	chr2:178584828;178584827;178584826	chr2:179449555;179449554;179449553
N2A	19037	57334;57335;57336	chr2:178584828;178584827;178584826	chr2:179449555;179449554;179449553
N2B	12540	37843;37844;37845	chr2:178584828;178584827;178584826	chr2:179449555;179449554;179449553
Novex-1	12665	38218;38219;38220	chr2:178584828;178584827;178584826	chr2:179449555;179449554;179449553
Novex-2	12732	38419;38420;38421	chr2:178584828;178584827;178584826	chr2:179449555;179449554;179449553
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGT
• RefSeq wild type template codon: CCA
• Domain: Fn3-44
• Domain position: 47
• Structural Position: 63
• Q(SASA): 0.4291
• 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/D	rs1553632971	None	1.0	N	0.631	0.459	0.29527378943	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
G/A	0.3576	ambiguous	0.3614	ambiguous	-0.585	Destabilizing	1.0	D	0.541	neutral	N	0.511691689	None	None	N
G/C	0.4967	ambiguous	0.4926	ambiguous	-0.768	Destabilizing	1.0	D	0.777	deleterious	N	0.501455364	None	None	N
G/D	0.4533	ambiguous	0.4862	ambiguous	-0.718	Destabilizing	1.0	D	0.631	neutral	N	0.457897277	None	None	N
G/E	0.4608	ambiguous	0.4895	ambiguous	-0.873	Destabilizing	1.0	D	0.725	prob.delet.	None	None	None	None	N
G/F	0.8932	likely_pathogenic	0.8947	pathogenic	-1.303	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
G/H	0.6807	likely_pathogenic	0.6992	pathogenic	-0.958	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
G/I	0.7743	likely_pathogenic	0.787	pathogenic	-0.613	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	N
G/K	0.5923	likely_pathogenic	0.6185	pathogenic	-0.937	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	N
G/L	0.7637	likely_pathogenic	0.7709	pathogenic	-0.613	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
G/M	0.7593	likely_pathogenic	0.7733	pathogenic	-0.411	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
G/N	0.466	ambiguous	0.4798	ambiguous	-0.475	Destabilizing	1.0	D	0.624	neutral	None	None	None	None	N
G/P	0.9201	likely_pathogenic	0.9288	pathogenic	-0.569	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
G/Q	0.4996	ambiguous	0.5274	ambiguous	-0.785	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
G/R	0.5033	ambiguous	0.5285	ambiguous	-0.493	Destabilizing	1.0	D	0.759	deleterious	N	0.472551008	None	None	N
G/S	0.2389	likely_benign	0.2423	benign	-0.652	Destabilizing	1.0	D	0.623	neutral	N	0.482984935	None	None	N
G/T	0.4496	ambiguous	0.4634	ambiguous	-0.741	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	N
G/V	0.6416	likely_pathogenic	0.655	pathogenic	-0.569	Destabilizing	1.0	D	0.767	deleterious	N	0.50926746	None	None	N
G/W	0.762	likely_pathogenic	0.7818	pathogenic	-1.464	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
G/Y	0.7643	likely_pathogenic	0.7791	pathogenic	-1.122	Destabilizing	1.0	D	0.76	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.