TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26249	78970;78971;78972	chr2:178567387;178567386;178567385	chr2:179432114;179432113;179432112
N2AB	24608	74047;74048;74049	chr2:178567387;178567386;178567385	chr2:179432114;179432113;179432112
N2A	23681	71266;71267;71268	chr2:178567387;178567386;178567385	chr2:179432114;179432113;179432112
N2B	17184	51775;51776;51777	chr2:178567387;178567386;178567385	chr2:179432114;179432113;179432112
Novex-1	17309	52150;52151;52152	chr2:178567387;178567386;178567385	chr2:179432114;179432113;179432112
Novex-2	17376	52351;52352;52353	chr2:178567387;178567386;178567385	chr2:179432114;179432113;179432112
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: Ig-137
• Domain position: 57
• Structural Position: 136
• Q(SASA): 0.104
• 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/T	None	None	1.0	N	0.743	0.3	None	gnomAD-4.0.0	1.63133E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.91187E-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	0.6235	likely_pathogenic	0.5925	pathogenic	-1.209	Destabilizing	1.0	D	0.772	deleterious	None	None	None	None	N
A/D	0.9713	likely_pathogenic	0.9682	pathogenic	-2.624	Highly Destabilizing	1.0	D	0.842	deleterious	N	0.515238135	None	None	N
A/E	0.9649	likely_pathogenic	0.9647	pathogenic	-2.417	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
A/F	0.8883	likely_pathogenic	0.8866	pathogenic	-0.609	Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
A/G	0.3058	likely_benign	0.2701	benign	-1.552	Destabilizing	1.0	D	0.575	neutral	N	0.457979343	None	None	N
A/H	0.9573	likely_pathogenic	0.958	pathogenic	-2.118	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
A/I	0.7847	likely_pathogenic	0.7721	pathogenic	0.268	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
A/K	0.9867	likely_pathogenic	0.9872	pathogenic	-1.224	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
A/L	0.6488	likely_pathogenic	0.6559	pathogenic	0.268	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
A/M	0.6448	likely_pathogenic	0.6406	pathogenic	0.01	Stabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
A/N	0.8852	likely_pathogenic	0.8821	pathogenic	-1.582	Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
A/P	0.9816	likely_pathogenic	0.9766	pathogenic	-0.133	Destabilizing	1.0	D	0.823	deleterious	N	0.463454022	None	None	N
A/Q	0.9444	likely_pathogenic	0.9467	pathogenic	-1.35	Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
A/R	0.9774	likely_pathogenic	0.9788	pathogenic	-1.368	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
A/S	0.1823	likely_benign	0.1729	benign	-1.945	Destabilizing	1.0	D	0.574	neutral	N	0.414591138	None	None	N
A/T	0.164	likely_benign	0.1527	benign	-1.616	Destabilizing	1.0	D	0.743	deleterious	N	0.390138197	None	None	N
A/V	0.4272	ambiguous	0.4001	ambiguous	-0.133	Destabilizing	1.0	D	0.633	neutral	N	0.502730197	None	None	N
A/W	0.9887	likely_pathogenic	0.9874	pathogenic	-1.504	Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
A/Y	0.9288	likely_pathogenic	0.9302	pathogenic	-0.945	Destabilizing	1.0	D	0.866	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.