TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16302	49129;49130;49131	chr2:178614610;178614609;178614608	chr2:179479337;179479336;179479335
N2AB	14661	44206;44207;44208	chr2:178614610;178614609;178614608	chr2:179479337;179479336;179479335
N2A	13734	41425;41426;41427	chr2:178614610;178614609;178614608	chr2:179479337;179479336;179479335
N2B	7237	21934;21935;21936	chr2:178614610;178614609;178614608	chr2:179479337;179479336;179479335
Novex-1	7362	22309;22310;22311	chr2:178614610;178614609;178614608	chr2:179479337;179479336;179479335
Novex-2	7429	22510;22511;22512	chr2:178614610;178614609;178614608	chr2:179479337;179479336;179479335
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-110
• Domain position: 41
• Structural Position: 73
• Q(SASA): 0.281
• 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	rs2056963801	None	1.0	N	0.456	0.202	0.245101548738	gnomAD-4.0.0	6.84735E-07	None	None	None	None	N	None	0	0	None	0	2.53254E-05	None	0	0	0	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	0.5947	likely_pathogenic	0.6625	pathogenic	-0.244	Destabilizing	1.0	D	0.775	deleterious	D	0.537666958	None	None	N
D/C	0.8641	likely_pathogenic	0.8778	pathogenic	-0.038	Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
D/E	0.4017	ambiguous	0.4608	ambiguous	-0.274	Destabilizing	1.0	D	0.456	neutral	N	0.452754387	None	None	N
D/F	0.9554	likely_pathogenic	0.968	pathogenic	-0.188	Destabilizing	1.0	D	0.829	deleterious	None	None	None	None	N
D/G	0.335	likely_benign	0.363	ambiguous	-0.434	Destabilizing	1.0	D	0.721	prob.delet.	N	0.442977029	None	None	N
D/H	0.7547	likely_pathogenic	0.7846	pathogenic	0.03	Stabilizing	1.0	D	0.749	deleterious	D	0.540211183	None	None	N
D/I	0.9133	likely_pathogenic	0.9352	pathogenic	0.206	Stabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
D/K	0.8772	likely_pathogenic	0.9075	pathogenic	0.254	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
D/L	0.8714	likely_pathogenic	0.8941	pathogenic	0.206	Stabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
D/M	0.936	likely_pathogenic	0.9488	pathogenic	0.261	Stabilizing	1.0	D	0.802	deleterious	None	None	None	None	N
D/N	0.1955	likely_benign	0.2134	benign	-0.015	Destabilizing	1.0	D	0.678	prob.neutral	N	0.44535671	None	None	N
D/P	0.9544	likely_pathogenic	0.9667	pathogenic	0.078	Stabilizing	1.0	D	0.756	deleterious	None	None	None	None	N
D/Q	0.7885	likely_pathogenic	0.8244	pathogenic	0.019	Stabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
D/R	0.9057	likely_pathogenic	0.9284	pathogenic	0.451	Stabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
D/S	0.3202	likely_benign	0.3563	ambiguous	-0.131	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
D/T	0.4846	ambiguous	0.5281	ambiguous	0.016	Stabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
D/V	0.753	likely_pathogenic	0.7996	pathogenic	0.078	Stabilizing	1.0	D	0.832	deleterious	D	0.572380626	None	None	N
D/W	0.9869	likely_pathogenic	0.9909	pathogenic	-0.071	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
D/Y	0.7623	likely_pathogenic	0.823	pathogenic	0.042	Stabilizing	1.0	D	0.817	deleterious	D	0.63411527	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.