TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24847	74764;74765;74766	chr2:178571593;178571592;178571591	chr2:179436320;179436319;179436318
N2AB	23206	69841;69842;69843	chr2:178571593;178571592;178571591	chr2:179436320;179436319;179436318
N2A	22279	67060;67061;67062	chr2:178571593;178571592;178571591	chr2:179436320;179436319;179436318
N2B	15782	47569;47570;47571	chr2:178571593;178571592;178571591	chr2:179436320;179436319;179436318
Novex-1	15907	47944;47945;47946	chr2:178571593;178571592;178571591	chr2:179436320;179436319;179436318
Novex-2	15974	48145;48146;48147	chr2:178571593;178571592;178571591	chr2:179436320;179436319;179436318
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-68
• Domain position: 40
• Structural Position: 41
• Q(SASA): 0.0937
• 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
E/K	None	None	0.999	D	0.667	0.48	0.422283790207	gnomAD-4.0.0	1.59262E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85979E-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
E/A	0.8267	likely_pathogenic	0.8248	pathogenic	-0.489	Destabilizing	0.999	D	0.733	prob.delet.	N	0.519062185	None	None	N
E/C	0.9764	likely_pathogenic	0.9729	pathogenic	0.171	Stabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
E/D	0.8932	likely_pathogenic	0.8908	pathogenic	-1.737	Destabilizing	0.999	D	0.667	neutral	N	0.476030047	None	None	N
E/F	0.9855	likely_pathogenic	0.9801	pathogenic	-0.322	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
E/G	0.9124	likely_pathogenic	0.9105	pathogenic	-0.869	Destabilizing	1.0	D	0.794	deleterious	N	0.520836612	None	None	N
E/H	0.9535	likely_pathogenic	0.9318	pathogenic	-0.211	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
E/I	0.9509	likely_pathogenic	0.9487	pathogenic	0.587	Stabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
E/K	0.8851	likely_pathogenic	0.8783	pathogenic	-0.473	Destabilizing	0.999	D	0.667	neutral	D	0.522567678	None	None	N
E/L	0.891	likely_pathogenic	0.8902	pathogenic	0.587	Stabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
E/M	0.8954	likely_pathogenic	0.8837	pathogenic	1.07	Stabilizing	1.0	D	0.801	deleterious	None	None	None	None	N
E/N	0.9729	likely_pathogenic	0.9712	pathogenic	-0.904	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
E/P	0.9997	likely_pathogenic	0.9997	pathogenic	0.245	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
E/Q	0.4671	ambiguous	0.4378	ambiguous	-0.556	Destabilizing	1.0	D	0.757	deleterious	N	0.479904558	None	None	N
E/R	0.94	likely_pathogenic	0.9328	pathogenic	-0.587	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
E/S	0.8994	likely_pathogenic	0.8894	pathogenic	-1.313	Destabilizing	0.999	D	0.72	prob.delet.	None	None	None	None	N
E/T	0.9477	likely_pathogenic	0.9439	pathogenic	-0.934	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/V	0.883	likely_pathogenic	0.8775	pathogenic	0.245	Stabilizing	1.0	D	0.805	deleterious	N	0.516201803	None	None	N
E/W	0.9942	likely_pathogenic	0.9911	pathogenic	-0.604	Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
E/Y	0.9792	likely_pathogenic	0.9706	pathogenic	-0.14	Destabilizing	1.0	D	0.826	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.