TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20675	62248;62249;62250	chr2:178589702;178589701;178589700	chr2:179454429;179454428;179454427
N2AB	19034	57325;57326;57327	chr2:178589702;178589701;178589700	chr2:179454429;179454428;179454427
N2A	18107	54544;54545;54546	chr2:178589702;178589701;178589700	chr2:179454429;179454428;179454427
N2B	11610	35053;35054;35055	chr2:178589702;178589701;178589700	chr2:179454429;179454428;179454427
Novex-1	11735	35428;35429;35430	chr2:178589702;178589701;178589700	chr2:179454429;179454428;179454427
Novex-2	11802	35629;35630;35631	chr2:178589702;178589701;178589700	chr2:179454429;179454428;179454427
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Fn3-38
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.1631
• 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
L/H	rs1432751152	-2.95	1.0	N	0.777	0.511	0.864692451478	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
L/H	rs1432751152	-2.95	1.0	N	0.777	0.511	0.864692451478	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
L/I	None	None	0.961	N	0.697	0.29	0.587237122171	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-06	0	3.66327E-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
L/A	0.9727	likely_pathogenic	0.9663	pathogenic	-2.452	Highly Destabilizing	0.985	D	0.718	prob.delet.	None	None	None	None	N
L/C	0.9204	likely_pathogenic	0.894	pathogenic	-1.755	Destabilizing	1.0	D	0.689	prob.neutral	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9993	pathogenic	-3.157	Highly Destabilizing	0.999	D	0.798	deleterious	None	None	None	None	N
L/E	0.9977	likely_pathogenic	0.9969	pathogenic	-2.946	Highly Destabilizing	0.999	D	0.795	deleterious	None	None	None	None	N
L/F	0.5524	ambiguous	0.4402	ambiguous	-1.421	Destabilizing	0.031	N	0.291	neutral	N	0.48264658	None	None	N
L/G	0.9946	likely_pathogenic	0.9936	pathogenic	-2.981	Highly Destabilizing	0.999	D	0.797	deleterious	None	None	None	None	N
L/H	0.9912	likely_pathogenic	0.9826	pathogenic	-2.632	Highly Destabilizing	1.0	D	0.777	deleterious	N	0.501542086	None	None	N
L/I	0.3116	likely_benign	0.2946	benign	-0.92	Destabilizing	0.961	D	0.697	prob.neutral	N	0.511486619	None	None	N
L/K	0.9938	likely_pathogenic	0.9894	pathogenic	-1.963	Destabilizing	0.999	D	0.77	deleterious	None	None	None	None	N
L/M	0.491	ambiguous	0.4247	ambiguous	-0.862	Destabilizing	0.999	D	0.701	prob.neutral	None	None	None	None	N
L/N	0.9965	likely_pathogenic	0.9942	pathogenic	-2.276	Highly Destabilizing	0.999	D	0.8	deleterious	None	None	None	None	N
L/P	0.9895	likely_pathogenic	0.9803	pathogenic	-1.413	Destabilizing	0.998	D	0.805	deleterious	N	0.404089795	None	None	N
L/Q	0.9901	likely_pathogenic	0.9843	pathogenic	-2.148	Highly Destabilizing	0.999	D	0.764	deleterious	None	None	None	None	N
L/R	0.9869	likely_pathogenic	0.98	pathogenic	-1.694	Destabilizing	0.998	D	0.752	deleterious	N	0.501542086	None	None	N
L/S	0.9959	likely_pathogenic	0.9941	pathogenic	-2.87	Highly Destabilizing	0.999	D	0.758	deleterious	None	None	None	None	N
L/T	0.9666	likely_pathogenic	0.9501	pathogenic	-2.526	Highly Destabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
L/V	0.3817	ambiguous	0.3666	ambiguous	-1.413	Destabilizing	0.961	D	0.722	prob.delet.	N	0.465826114	None	None	N
L/W	0.9628	likely_pathogenic	0.9378	pathogenic	-1.945	Destabilizing	1.0	D	0.738	prob.delet.	None	None	None	None	N
L/Y	0.9627	likely_pathogenic	0.9406	pathogenic	-1.642	Destabilizing	0.942	D	0.75	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.