TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33166	99721;99722;99723	chr2:178537711;178537710;178537709	chr2:179402438;179402437;179402436
N2AB	31525	94798;94799;94800	chr2:178537711;178537710;178537709	chr2:179402438;179402437;179402436
N2A	30598	92017;92018;92019	chr2:178537711;178537710;178537709	chr2:179402438;179402437;179402436
N2B	24101	72526;72527;72528	chr2:178537711;178537710;178537709	chr2:179402438;179402437;179402436
Novex-1	24226	72901;72902;72903	chr2:178537711;178537710;178537709	chr2:179402438;179402437;179402436
Novex-2	24293	73102;73103;73104	chr2:178537711;178537710;178537709	chr2:179402438;179402437;179402436
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-156
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.2573
• 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
E/G	None	None	0.998	N	0.617	0.458	0.351830644314	gnomAD-4.0.0	1.59131E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85824E-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	0.3432	ambiguous	0.4303	ambiguous	-0.447	Destabilizing	0.972	D	0.642	neutral	N	0.512064544	None	None	N
E/C	0.9704	likely_pathogenic	0.977	pathogenic	-0.101	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
E/D	0.317	likely_benign	0.3868	ambiguous	-0.388	Destabilizing	0.014	N	0.244	neutral	N	0.480125484	None	None	N
E/F	0.9559	likely_pathogenic	0.9715	pathogenic	-0.312	Destabilizing	1.0	D	0.747	deleterious	None	None	None	None	N
E/G	0.3615	ambiguous	0.4699	ambiguous	-0.647	Destabilizing	0.998	D	0.617	neutral	N	0.515374208	None	None	N
E/H	0.8958	likely_pathogenic	0.9219	pathogenic	-0.081	Destabilizing	1.0	D	0.719	prob.delet.	None	None	None	None	N
E/I	0.7513	likely_pathogenic	0.8252	pathogenic	0.049	Stabilizing	0.996	D	0.753	deleterious	None	None	None	None	N
E/K	0.5387	ambiguous	0.6411	pathogenic	0.246	Stabilizing	0.985	D	0.593	neutral	N	0.497865882	None	None	N
E/L	0.8102	likely_pathogenic	0.8727	pathogenic	0.049	Stabilizing	0.996	D	0.732	prob.delet.	None	None	None	None	N
E/M	0.7932	likely_pathogenic	0.8517	pathogenic	0.16	Stabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
E/N	0.6525	likely_pathogenic	0.7493	pathogenic	-0.091	Destabilizing	0.97	D	0.717	prob.delet.	None	None	None	None	N
E/P	0.9482	likely_pathogenic	0.9479	pathogenic	-0.097	Destabilizing	0.977	D	0.707	prob.neutral	None	None	None	None	N
E/Q	0.4405	ambiguous	0.5218	ambiguous	-0.056	Destabilizing	0.997	D	0.661	neutral	N	0.514912848	None	None	N
E/R	0.7041	likely_pathogenic	0.7719	pathogenic	0.467	Stabilizing	0.998	D	0.72	prob.delet.	None	None	None	None	N
E/S	0.5181	ambiguous	0.6292	pathogenic	-0.255	Destabilizing	0.979	D	0.623	neutral	None	None	None	None	N
E/T	0.5763	likely_pathogenic	0.672	pathogenic	-0.09	Destabilizing	0.995	D	0.685	prob.neutral	None	None	None	None	N
E/V	0.5665	likely_pathogenic	0.659	pathogenic	-0.097	Destabilizing	0.993	D	0.705	prob.neutral	N	0.459356326	None	None	N
E/W	0.98	likely_pathogenic	0.9866	pathogenic	-0.151	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
E/Y	0.9259	likely_pathogenic	0.946	pathogenic	-0.071	Destabilizing	1.0	D	0.721	prob.delet.	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.