TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16272	49039;49040;49041	chr2:178614700;178614699;178614698	chr2:179479427;179479426;179479425
N2AB	14631	44116;44117;44118	chr2:178614700;178614699;178614698	chr2:179479427;179479426;179479425
N2A	13704	41335;41336;41337	chr2:178614700;178614699;178614698	chr2:179479427;179479426;179479425
N2B	7207	21844;21845;21846	chr2:178614700;178614699;178614698	chr2:179479427;179479426;179479425
Novex-1	7332	22219;22220;22221	chr2:178614700;178614699;178614698	chr2:179479427;179479426;179479425
Novex-2	7399	22420;22421;22422	chr2:178614700;178614699;178614698	chr2:179479427;179479426;179479425
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-110
• Domain position: 11
• Structural Position: 23
• Q(SASA): 0.517
• 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	0.721	0.276	0.238096912614	gnomAD-4.0.0	1.59525E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86441E-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	0.8497	likely_pathogenic	0.8121	pathogenic	-0.807	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
A/D	0.9602	likely_pathogenic	0.9504	pathogenic	-0.845	Destabilizing	1.0	D	0.793	deleterious	N	0.506647873	None	None	N
A/E	0.8547	likely_pathogenic	0.8303	pathogenic	-0.992	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
A/F	0.9401	likely_pathogenic	0.9136	pathogenic	-1.158	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
A/G	0.5708	likely_pathogenic	0.522	ambiguous	-0.66	Destabilizing	1.0	D	0.549	neutral	D	0.596073975	None	None	N
A/H	0.9443	likely_pathogenic	0.924	pathogenic	-0.7	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
A/I	0.8024	likely_pathogenic	0.7509	pathogenic	-0.529	Destabilizing	1.0	D	0.745	deleterious	None	None	None	None	N
A/K	0.9315	likely_pathogenic	0.9207	pathogenic	-0.827	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
A/L	0.8061	likely_pathogenic	0.7747	pathogenic	-0.529	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
A/M	0.7809	likely_pathogenic	0.7422	pathogenic	-0.35	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	N
A/N	0.876	likely_pathogenic	0.852	pathogenic	-0.481	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
A/P	0.9617	likely_pathogenic	0.9445	pathogenic	-0.509	Destabilizing	1.0	D	0.767	deleterious	N	0.44252616	None	None	N
A/Q	0.8027	likely_pathogenic	0.7754	pathogenic	-0.819	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
A/R	0.8841	likely_pathogenic	0.8653	pathogenic	-0.308	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
A/S	0.2438	likely_benign	0.2203	benign	-0.701	Destabilizing	1.0	D	0.557	neutral	N	0.45111894	None	None	N
A/T	0.5277	ambiguous	0.469	ambiguous	-0.776	Destabilizing	1.0	D	0.721	prob.delet.	N	0.482765378	None	None	N
A/V	0.4377	ambiguous	0.3859	ambiguous	-0.509	Destabilizing	1.0	D	0.642	neutral	N	0.444853666	None	None	N
A/W	0.9925	likely_pathogenic	0.9883	pathogenic	-1.285	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
A/Y	0.9574	likely_pathogenic	0.9377	pathogenic	-0.942	Destabilizing	1.0	D	0.795	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.