TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1491	4696;4697;4698	chr2:178777713;178777712;178777711	chr2:179642440;179642439;179642438
N2AB	1491	4696;4697;4698	chr2:178777713;178777712;178777711	chr2:179642440;179642439;179642438
N2A	1491	4696;4697;4698	chr2:178777713;178777712;178777711	chr2:179642440;179642439;179642438
N2B	1445	4558;4559;4560	chr2:178777713;178777712;178777711	chr2:179642440;179642439;179642438
Novex-1	1445	4558;4559;4560	chr2:178777713;178777712;178777711	chr2:179642440;179642439;179642438
Novex-2	1445	4558;4559;4560	chr2:178777713;178777712;178777711	chr2:179642440;179642439;179642438
Novex-3	1491	4696;4697;4698	chr2:178777713;178777712;178777711	chr2:179642440;179642439;179642438

Information

• RefSeq wild type amino acid: F
• RefSeq wild type transcript codon: TTT
• RefSeq wild type template codon: AAA
• Domain: Ig-6
• Domain position: 35
• Structural Position: 49
• Q(SASA): 0.1787
• 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
F/L	None	None	0.999	N	0.581	0.71	0.659362306107	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
F/A	0.9806	likely_pathogenic	0.9822	pathogenic	-2.559	Highly Destabilizing	1.0	D	0.752	deleterious	None	None	None	None	N
F/C	0.8767	likely_pathogenic	0.8801	pathogenic	-1.427	Destabilizing	1.0	D	0.807	deleterious	D	0.722000431	None	None	N
F/D	0.9943	likely_pathogenic	0.9943	pathogenic	-1.908	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
F/E	0.9881	likely_pathogenic	0.9888	pathogenic	-1.752	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
F/G	0.9893	likely_pathogenic	0.9897	pathogenic	-2.95	Highly Destabilizing	1.0	D	0.805	deleterious	None	None	None	None	N
F/H	0.8566	likely_pathogenic	0.8583	pathogenic	-1.25	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
F/I	0.7505	likely_pathogenic	0.7774	pathogenic	-1.327	Destabilizing	1.0	D	0.746	deleterious	D	0.530773552	None	None	N
F/K	0.9842	likely_pathogenic	0.9853	pathogenic	-1.484	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
F/L	0.9685	likely_pathogenic	0.9711	pathogenic	-1.327	Destabilizing	0.999	D	0.581	neutral	N	0.495897433	None	None	N
F/M	0.8762	likely_pathogenic	0.8911	pathogenic	-1.061	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
F/N	0.9586	likely_pathogenic	0.9607	pathogenic	-1.693	Destabilizing	1.0	D	0.835	deleterious	None	None	None	None	N
F/P	0.9999	likely_pathogenic	0.9999	pathogenic	-1.741	Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
F/Q	0.9653	likely_pathogenic	0.9657	pathogenic	-1.733	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
F/R	0.9606	likely_pathogenic	0.9624	pathogenic	-0.901	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
F/S	0.9463	likely_pathogenic	0.9477	pathogenic	-2.483	Highly Destabilizing	1.0	D	0.809	deleterious	D	0.536337113	None	None	N
F/T	0.9643	likely_pathogenic	0.9669	pathogenic	-2.231	Highly Destabilizing	1.0	D	0.812	deleterious	None	None	None	None	N
F/V	0.7988	likely_pathogenic	0.8144	pathogenic	-1.741	Destabilizing	1.0	D	0.765	deleterious	D	0.60957921	None	None	N
F/W	0.7553	likely_pathogenic	0.7745	pathogenic	-0.263	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
F/Y	0.228	likely_benign	0.2351	benign	-0.561	Destabilizing	0.999	D	0.513	neutral	N	0.499988034	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.