TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24459	73600;73601;73602	chr2:178572757;178572756;178572755	chr2:179437484;179437483;179437482
N2AB	22818	68677;68678;68679	chr2:178572757;178572756;178572755	chr2:179437484;179437483;179437482
N2A	21891	65896;65897;65898	chr2:178572757;178572756;178572755	chr2:179437484;179437483;179437482
N2B	15394	46405;46406;46407	chr2:178572757;178572756;178572755	chr2:179437484;179437483;179437482
Novex-1	15519	46780;46781;46782	chr2:178572757;178572756;178572755	chr2:179437484;179437483;179437482
Novex-2	15586	46981;46982;46983	chr2:178572757;178572756;178572755	chr2:179437484;179437483;179437482
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Ig-132
• Domain position: 29
• Structural Position: 45
• Q(SASA): 0.651
• 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	0.892	D	0.556	0.5	0.671833516112	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
E/K	rs1446425983	None	0.892	N	0.541	0.325	0.458101713262	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
E/K	rs1446425983	None	0.892	N	0.541	0.325	0.458101713262	gnomAD-4.0.0	4.33869E-06	None	None	None	None	I	None	1.33529E-05	0	None	0	0	None	0	0	4.2387E-06	0	1.60128E-05

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	0.1458	likely_benign	0.1598	benign	-0.352	Destabilizing	0.892	D	0.591	neutral	N	0.498027048	None	None	I
E/C	0.8101	likely_pathogenic	0.8246	pathogenic	-0.135	Destabilizing	0.999	D	0.752	deleterious	None	None	None	None	I
E/D	0.1284	likely_benign	0.1487	benign	-0.446	Destabilizing	0.011	N	0.252	neutral	N	0.497266579	None	None	I
E/F	0.7604	likely_pathogenic	0.7829	pathogenic	-0.247	Destabilizing	0.999	D	0.708	prob.delet.	None	None	None	None	I
E/G	0.258	likely_benign	0.2802	benign	-0.563	Destabilizing	0.892	D	0.556	neutral	D	0.531388402	None	None	I
E/H	0.4097	ambiguous	0.4258	ambiguous	-0.081	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	I
E/I	0.2542	likely_benign	0.2792	benign	0.172	Stabilizing	0.987	D	0.724	prob.delet.	None	None	None	None	I
E/K	0.1399	likely_benign	0.1485	benign	0.093	Stabilizing	0.892	D	0.541	neutral	N	0.487113824	None	None	I
E/L	0.3303	likely_benign	0.3489	ambiguous	0.172	Stabilizing	0.987	D	0.71	prob.delet.	None	None	None	None	I
E/M	0.3877	ambiguous	0.4097	ambiguous	0.212	Stabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	I
E/N	0.2072	likely_benign	0.2398	benign	-0.13	Destabilizing	0.95	D	0.597	neutral	None	None	None	None	I
E/P	0.9023	likely_pathogenic	0.9147	pathogenic	0.018	Stabilizing	0.987	D	0.678	prob.neutral	None	None	None	None	I
E/Q	0.1325	likely_benign	0.132	benign	-0.094	Destabilizing	0.983	D	0.577	neutral	D	0.536579852	None	None	I
E/R	0.2542	likely_benign	0.2638	benign	0.33	Stabilizing	0.987	D	0.641	neutral	None	None	None	None	I
E/S	0.1805	likely_benign	0.1954	benign	-0.314	Destabilizing	0.916	D	0.543	neutral	None	None	None	None	I
E/T	0.1619	likely_benign	0.1728	benign	-0.151	Destabilizing	0.975	D	0.619	neutral	None	None	None	None	I
E/V	0.1534	likely_benign	0.1617	benign	0.018	Stabilizing	0.983	D	0.673	neutral	N	0.48832981	None	None	I
E/W	0.917	likely_pathogenic	0.9248	pathogenic	-0.127	Destabilizing	0.999	D	0.753	deleterious	None	None	None	None	I
E/Y	0.637	likely_pathogenic	0.6685	pathogenic	-0.022	Destabilizing	0.999	D	0.695	prob.neutral	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.