TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6984	21175;21176;21177	chr2:178724425;178724424;178724423	chr2:179589152;179589151;179589150
N2AB	6667	20224;20225;20226	chr2:178724425;178724424;178724423	chr2:179589152;179589151;179589150
N2A	5740	17443;17444;17445	chr2:178724425;178724424;178724423	chr2:179589152;179589151;179589150
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-54
• Domain position: 37
• Structural Position: 51
• Q(SASA): 0.8481
• 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
D/N	None	None	0.801	N	0.421	0.255	0.136095386433	gnomAD-4.0.0	1.59206E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43295E-05	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
D/A	0.3043	likely_benign	0.2894	benign	-0.572	Destabilizing	0.022	N	0.225	neutral	N	0.47585442	None	None	N
D/C	0.776	likely_pathogenic	0.7753	pathogenic	-0.167	Destabilizing	0.998	D	0.435	neutral	None	None	None	None	N
D/E	0.2828	likely_benign	0.2932	benign	-0.407	Destabilizing	0.012	N	0.235	neutral	N	0.460090341	None	None	N
D/F	0.7888	likely_pathogenic	0.7977	pathogenic	-0.248	Destabilizing	0.991	D	0.436	neutral	None	None	None	None	N
D/G	0.1977	likely_benign	0.187	benign	-0.829	Destabilizing	0.005	N	0.213	neutral	N	0.454770742	None	None	N
D/H	0.4594	ambiguous	0.4641	ambiguous	-0.18	Destabilizing	0.966	D	0.374	neutral	N	0.498086505	None	None	N
D/I	0.8088	likely_pathogenic	0.7899	pathogenic	0.081	Stabilizing	0.974	D	0.45	neutral	None	None	None	None	N
D/K	0.6365	likely_pathogenic	0.6416	pathogenic	0.047	Stabilizing	0.728	D	0.418	neutral	None	None	None	None	N
D/L	0.6978	likely_pathogenic	0.6907	pathogenic	0.081	Stabilizing	0.842	D	0.443	neutral	None	None	None	None	N
D/M	0.8494	likely_pathogenic	0.8351	pathogenic	0.319	Stabilizing	0.998	D	0.431	neutral	None	None	None	None	N
D/N	0.11	likely_benign	0.102	benign	-0.401	Destabilizing	0.801	D	0.421	neutral	N	0.4648466	None	None	N
D/P	0.9887	likely_pathogenic	0.9838	pathogenic	-0.114	Destabilizing	0.974	D	0.377	neutral	None	None	None	None	N
D/Q	0.5448	ambiguous	0.5372	ambiguous	-0.324	Destabilizing	0.904	D	0.346	neutral	None	None	None	None	N
D/R	0.6259	likely_pathogenic	0.6289	pathogenic	0.294	Stabilizing	0.949	D	0.425	neutral	None	None	None	None	N
D/S	0.2297	likely_benign	0.2093	benign	-0.541	Destabilizing	0.525	D	0.37	neutral	None	None	None	None	N
D/T	0.6396	likely_pathogenic	0.6028	pathogenic	-0.329	Destabilizing	0.842	D	0.418	neutral	None	None	None	None	N
D/V	0.5711	likely_pathogenic	0.5576	ambiguous	-0.114	Destabilizing	0.801	D	0.463	neutral	N	0.489123283	None	None	N
D/W	0.9369	likely_pathogenic	0.9361	pathogenic	-0.008	Destabilizing	0.998	D	0.521	neutral	None	None	None	None	N
D/Y	0.3255	likely_benign	0.3354	benign	0.011	Stabilizing	0.989	D	0.433	neutral	N	0.503112934	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.