TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23934	72025;72026;72027	chr2:178574332;178574331;178574330	chr2:179439059;179439058;179439057
N2AB	22293	67102;67103;67104	chr2:178574332;178574331;178574330	chr2:179439059;179439058;179439057
N2A	21366	64321;64322;64323	chr2:178574332;178574331;178574330	chr2:179439059;179439058;179439057
N2B	14869	44830;44831;44832	chr2:178574332;178574331;178574330	chr2:179439059;179439058;179439057
Novex-1	14994	45205;45206;45207	chr2:178574332;178574331;178574330	chr2:179439059;179439058;179439057
Novex-2	15061	45406;45407;45408	chr2:178574332;178574331;178574330	chr2:179439059;179439058;179439057
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-62
• Domain position: 11
• Structural Position: 13
• Q(SASA): 0.3656
• 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/V	rs1465413205	None	0.76	N	0.435	0.092	0.250579442822	gnomAD-4.0.0	1.36858E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.15955E-05	1.65673E-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	0.1989	likely_benign	0.2239	benign	-1.114	Destabilizing	0.953	D	0.531	neutral	None	None	None	None	N
L/C	0.4321	ambiguous	0.4622	ambiguous	-0.7	Destabilizing	0.999	D	0.656	neutral	None	None	None	None	N
L/D	0.6501	likely_pathogenic	0.7089	pathogenic	-0.526	Destabilizing	0.993	D	0.745	deleterious	None	None	None	None	N
L/E	0.2688	likely_benign	0.3113	benign	-0.566	Destabilizing	0.993	D	0.74	deleterious	None	None	None	None	N
L/F	0.1374	likely_benign	0.1538	benign	-0.795	Destabilizing	0.986	D	0.603	neutral	None	None	None	None	N
L/G	0.4708	ambiguous	0.52	ambiguous	-1.369	Destabilizing	0.993	D	0.744	deleterious	None	None	None	None	N
L/H	0.2157	likely_benign	0.2506	benign	-0.51	Destabilizing	0.999	D	0.716	prob.delet.	None	None	None	None	N
L/I	0.0693	likely_benign	0.0727	benign	-0.523	Destabilizing	0.1	N	0.197	neutral	N	0.443213039	None	None	N
L/K	0.2512	likely_benign	0.2767	benign	-0.722	Destabilizing	0.993	D	0.726	prob.delet.	None	None	None	None	N
L/M	0.1056	likely_benign	0.1128	benign	-0.482	Destabilizing	0.986	D	0.593	neutral	None	None	None	None	N
L/N	0.3496	ambiguous	0.3962	ambiguous	-0.517	Destabilizing	0.993	D	0.746	deleterious	None	None	None	None	N
L/P	0.8352	likely_pathogenic	0.847	pathogenic	-0.687	Destabilizing	0.997	D	0.748	deleterious	N	0.473192437	None	None	N
L/Q	0.1275	likely_benign	0.141	benign	-0.714	Destabilizing	0.997	D	0.716	prob.delet.	N	0.503434778	None	None	N
L/R	0.1856	likely_benign	0.2088	benign	-0.113	Destabilizing	0.991	D	0.719	prob.delet.	N	0.46664507	None	None	N
L/S	0.2229	likely_benign	0.2594	benign	-1.053	Destabilizing	0.973	D	0.625	neutral	None	None	None	None	N
L/T	0.1551	likely_benign	0.1654	benign	-0.978	Destabilizing	0.386	N	0.251	neutral	None	None	None	None	N
L/V	0.0687	likely_benign	0.0721	benign	-0.687	Destabilizing	0.76	D	0.435	neutral	N	0.427763584	None	None	N
L/W	0.2893	likely_benign	0.3312	benign	-0.826	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
L/Y	0.3449	ambiguous	0.3901	ambiguous	-0.603	Destabilizing	0.998	D	0.698	prob.neutral	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.