TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35789	107590;107591;107592	chr2:178528286;178528285;178528284	chr2:179393013;179393012;179393011
N2AB	34148	102667;102668;102669	chr2:178528286;178528285;178528284	chr2:179393013;179393012;179393011
N2A	33221	99886;99887;99888	chr2:178528286;178528285;178528284	chr2:179393013;179393012;179393011
N2B	26724	80395;80396;80397	chr2:178528286;178528285;178528284	chr2:179393013;179393012;179393011
Novex-1	26849	80770;80771;80772	chr2:178528286;178528285;178528284	chr2:179393013;179393012;179393011
Novex-2	26916	80971;80972;80973	chr2:178528286;178528285;178528284	chr2:179393013;179393012;179393011
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTA
• RefSeq wild type template codon: AAT
• Domain: Ig-168
• Domain position: 88
• Structural Position: 174
• Q(SASA): 0.157
• 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/S	None	None	1.0	D	0.853	0.666	0.825594158583	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
L/A	0.9241	likely_pathogenic	0.939	pathogenic	-2.822	Highly Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	N
L/C	0.9442	likely_pathogenic	0.955	pathogenic	-2.4	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
L/D	0.9993	likely_pathogenic	0.9995	pathogenic	-3.165	Highly Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
L/E	0.9943	likely_pathogenic	0.9961	pathogenic	-2.895	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/F	0.7544	likely_pathogenic	0.7933	pathogenic	-1.787	Destabilizing	1.0	D	0.782	deleterious	N	0.52046558	None	None	N
L/G	0.991	likely_pathogenic	0.993	pathogenic	-3.421	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
L/H	0.9888	likely_pathogenic	0.9927	pathogenic	-2.913	Highly Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
L/I	0.2126	likely_benign	0.2736	benign	-1.06	Destabilizing	0.999	D	0.584	neutral	N	0.48984925	None	None	N
L/K	0.9915	likely_pathogenic	0.9943	pathogenic	-2.136	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
L/M	0.4039	ambiguous	0.465	ambiguous	-1.192	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
L/N	0.9948	likely_pathogenic	0.997	pathogenic	-2.631	Highly Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
L/P	0.9967	likely_pathogenic	0.9978	pathogenic	-1.632	Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
L/Q	0.978	likely_pathogenic	0.985	pathogenic	-2.415	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
L/R	0.9816	likely_pathogenic	0.9866	pathogenic	-1.95	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
L/S	0.9883	likely_pathogenic	0.9923	pathogenic	-3.382	Highly Destabilizing	1.0	D	0.853	deleterious	D	0.555966528	None	None	N
L/T	0.9497	likely_pathogenic	0.9674	pathogenic	-2.945	Highly Destabilizing	1.0	D	0.82	deleterious	None	None	None	None	N
L/V	0.2212	likely_benign	0.2747	benign	-1.632	Destabilizing	0.999	D	0.585	neutral	N	0.47128356	None	None	N
L/W	0.9849	likely_pathogenic	0.9891	pathogenic	-2.158	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
L/Y	0.9859	likely_pathogenic	0.989	pathogenic	-1.91	Destabilizing	1.0	D	0.82	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.