TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14246	42961;42962;42963	chr2:178633623;178633622;178633621	chr2:179498350;179498349;179498348
N2AB	12605	38038;38039;38040	chr2:178633623;178633622;178633621	chr2:179498350;179498349;179498348
N2A	11678	35257;35258;35259	chr2:178633623;178633622;178633621	chr2:179498350;179498349;179498348
N2B	5181	15766;15767;15768	chr2:178633623;178633622;178633621	chr2:179498350;179498349;179498348
Novex-1	5306	16141;16142;16143	chr2:178633623;178633622;178633621	chr2:179498350;179498349;179498348
Novex-2	5373	16342;16343;16344	chr2:178633623;178633622;178633621	chr2:179498350;179498349;179498348
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Ig-93
• Domain position: 16
• Structural Position: 25
• Q(SASA): 0.3616
• 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
D/E	None	None	0.928	N	0.439	0.104	0.134241683229	gnomAD-4.0.0	1.36946E-06	None	None	None	None	N	None	2.99115E-05	0	None	0	0	None	0	0	8.9993E-07	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
D/A	0.3685	ambiguous	0.2646	benign	-0.453	Destabilizing	0.978	D	0.681	prob.neutral	N	0.468373354	None	None	N
D/C	0.9292	likely_pathogenic	0.8567	pathogenic	-0.051	Destabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
D/E	0.2692	likely_benign	0.2059	benign	-0.508	Destabilizing	0.928	D	0.439	neutral	N	0.438953191	None	None	N
D/F	0.9211	likely_pathogenic	0.8292	pathogenic	-0.226	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
D/G	0.3079	likely_benign	0.2046	benign	-0.731	Destabilizing	0.865	D	0.614	neutral	N	0.447376727	None	None	N
D/H	0.7004	likely_pathogenic	0.5539	ambiguous	-0.362	Destabilizing	0.994	D	0.74	deleterious	N	0.508014656	None	None	N
D/I	0.859	likely_pathogenic	0.6787	pathogenic	0.255	Stabilizing	0.992	D	0.773	deleterious	None	None	None	None	N
D/K	0.7094	likely_pathogenic	0.5744	pathogenic	0.069	Stabilizing	0.968	D	0.702	prob.neutral	None	None	None	None	N
D/L	0.8126	likely_pathogenic	0.6561	pathogenic	0.255	Stabilizing	0.992	D	0.745	deleterious	None	None	None	None	N
D/M	0.8805	likely_pathogenic	0.7844	pathogenic	0.545	Stabilizing	0.999	D	0.756	deleterious	None	None	None	None	N
D/N	0.2268	likely_benign	0.1389	benign	-0.363	Destabilizing	0.085	N	0.363	neutral	N	0.474976619	None	None	N
D/P	0.988	likely_pathogenic	0.9601	pathogenic	0.043	Stabilizing	0.992	D	0.745	deleterious	None	None	None	None	N
D/Q	0.5853	likely_pathogenic	0.5086	ambiguous	-0.285	Destabilizing	0.983	D	0.733	prob.delet.	None	None	None	None	N
D/R	0.7894	likely_pathogenic	0.6556	pathogenic	0.198	Stabilizing	0.983	D	0.745	deleterious	None	None	None	None	N
D/S	0.2831	likely_benign	0.1948	benign	-0.504	Destabilizing	0.895	D	0.609	neutral	None	None	None	None	N
D/T	0.5271	ambiguous	0.3876	ambiguous	-0.281	Destabilizing	0.983	D	0.705	prob.neutral	None	None	None	None	N
D/V	0.6592	likely_pathogenic	0.4331	ambiguous	0.043	Stabilizing	0.989	D	0.745	deleterious	D	0.63322468	None	None	N
D/W	0.9765	likely_pathogenic	0.9517	pathogenic	-0.045	Destabilizing	0.999	D	0.757	deleterious	None	None	None	None	N
D/Y	0.5861	likely_pathogenic	0.4047	ambiguous	0.023	Stabilizing	0.999	D	0.758	deleterious	D	0.5470707	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.