TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1527	4804;4805;4806	chr2:178777486;178777485;178777484	chr2:179642213;179642212;179642211
N2AB	1527	4804;4805;4806	chr2:178777486;178777485;178777484	chr2:179642213;179642212;179642211
N2A	1527	4804;4805;4806	chr2:178777486;178777485;178777484	chr2:179642213;179642212;179642211
N2B	1481	4666;4667;4668	chr2:178777486;178777485;178777484	chr2:179642213;179642212;179642211
Novex-1	1481	4666;4667;4668	chr2:178777486;178777485;178777484	chr2:179642213;179642212;179642211
Novex-2	1481	4666;4667;4668	chr2:178777486;178777485;178777484	chr2:179642213;179642212;179642211
Novex-3	1527	4804;4805;4806	chr2:178777486;178777485;178777484	chr2:179642213;179642212;179642211

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-6
• Domain position: 71
• Structural Position: 153
• Q(SASA): 0.6481
• Predicted PPI site: I

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/G	None	None	1.0	D	0.76	0.7	0.718278560113	gnomAD-4.0.0	1.59098E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85695E-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	0.1793	likely_benign	0.1965	benign	-0.802	Destabilizing	0.999	D	0.71	prob.delet.	N	0.511977946	None	None	I
E/C	0.8656	likely_pathogenic	0.8852	pathogenic	-0.281	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	I
E/D	0.1879	likely_benign	0.2217	benign	-0.988	Destabilizing	0.999	D	0.553	neutral	D	0.5747723	None	None	I
E/F	0.7575	likely_pathogenic	0.7926	pathogenic	-0.758	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	I
E/G	0.2978	likely_benign	0.3312	benign	-1.105	Destabilizing	1.0	D	0.76	deleterious	D	0.71345337	None	None	I
E/H	0.4793	ambiguous	0.5223	ambiguous	-1.107	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
E/I	0.3098	likely_benign	0.3392	benign	0.004	Stabilizing	1.0	D	0.805	deleterious	None	None	None	None	I
E/K	0.13	likely_benign	0.1421	benign	-0.422	Destabilizing	0.999	D	0.65	neutral	N	0.502167825	None	None	I
E/L	0.3573	ambiguous	0.4001	ambiguous	0.004	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	I
E/M	0.4178	ambiguous	0.4523	ambiguous	0.531	Stabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
E/N	0.2283	likely_benign	0.2783	benign	-0.726	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
E/P	0.6794	likely_pathogenic	0.715	pathogenic	-0.244	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
E/Q	0.1366	likely_benign	0.1502	benign	-0.65	Destabilizing	1.0	D	0.635	neutral	N	0.509020124	None	None	I
E/R	0.2639	likely_benign	0.2824	benign	-0.362	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
E/S	0.212	likely_benign	0.2511	benign	-1.014	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
E/T	0.1983	likely_benign	0.2267	benign	-0.763	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
E/V	0.2034	likely_benign	0.2224	benign	-0.244	Destabilizing	1.0	D	0.793	deleterious	N	0.511074059	None	None	I
E/W	0.9323	likely_pathogenic	0.9427	pathogenic	-0.648	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
E/Y	0.6775	likely_pathogenic	0.7151	pathogenic	-0.534	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I

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.