TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23093	69502;69503;69504	chr2:178577058;178577057;178577056	chr2:179441785;179441784;179441783
N2AB	21452	64579;64580;64581	chr2:178577058;178577057;178577056	chr2:179441785;179441784;179441783
N2A	20525	61798;61799;61800	chr2:178577058;178577057;178577056	chr2:179441785;179441784;179441783
N2B	14028	42307;42308;42309	chr2:178577058;178577057;178577056	chr2:179441785;179441784;179441783
Novex-1	14153	42682;42683;42684	chr2:178577058;178577057;178577056	chr2:179441785;179441784;179441783
Novex-2	14220	42883;42884;42885	chr2:178577058;178577057;178577056	chr2:179441785;179441784;179441783
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: Fn3-55
• Domain position: 54
• Structural Position: 75
• Q(SASA): 0.7069
• Predicted PPI site: I

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/G	None	None	0.001	N	0.108	0.149	0.132336055621	gnomAD-4.0.0	4.80129E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	5.25001E-06	0	0
D/N	None	None	None	N	0.104	0.075	0.119812018005	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-06	0	0
D/V	None	None	0.491	N	0.39	0.248	0.477762074677	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
D/A	0.1502	likely_benign	0.1328	benign	-0.389	Destabilizing	0.166	N	0.332	neutral	N	0.468130126	None	None	I
D/C	0.5273	ambiguous	0.4838	ambiguous	-0.093	Destabilizing	0.991	D	0.332	neutral	None	None	None	None	I
D/E	0.1163	likely_benign	0.1087	benign	-0.352	Destabilizing	0.285	N	0.278	neutral	N	0.445695984	None	None	I
D/F	0.5203	ambiguous	0.468	ambiguous	-0.169	Destabilizing	0.901	D	0.357	neutral	None	None	None	None	I
D/G	0.1219	likely_benign	0.1008	benign	-0.636	Destabilizing	0.001	N	0.108	neutral	N	0.454835542	None	None	I
D/H	0.209	likely_benign	0.2	benign	-0.2	Destabilizing	0.873	D	0.341	neutral	N	0.472402582	None	None	I
D/I	0.3132	likely_benign	0.2878	benign	0.23	Stabilizing	0.901	D	0.385	neutral	None	None	None	None	I
D/K	0.2838	likely_benign	0.2571	benign	0.068	Stabilizing	0.561	D	0.338	neutral	None	None	None	None	I
D/L	0.3679	ambiguous	0.3344	benign	0.23	Stabilizing	0.561	D	0.411	neutral	None	None	None	None	I
D/M	0.4502	ambiguous	0.4196	ambiguous	0.417	Stabilizing	0.991	D	0.331	neutral	None	None	None	None	I
D/N	0.0704	likely_benign	0.0696	benign	-0.274	Destabilizing	None	N	0.104	neutral	N	0.439732804	None	None	I
D/P	0.6581	likely_pathogenic	0.6029	pathogenic	0.047	Stabilizing	0.722	D	0.421	neutral	None	None	None	None	I
D/Q	0.2387	likely_benign	0.2221	benign	-0.206	Destabilizing	0.561	D	0.335	neutral	None	None	None	None	I
D/R	0.3577	ambiguous	0.3253	benign	0.244	Stabilizing	0.561	D	0.375	neutral	None	None	None	None	I
D/S	0.1147	likely_benign	0.1091	benign	-0.415	Destabilizing	0.007	N	0.089	neutral	None	None	None	None	I
D/T	0.1687	likely_benign	0.1604	benign	-0.219	Destabilizing	0.209	N	0.325	neutral	None	None	None	None	I
D/V	0.2001	likely_benign	0.1853	benign	0.047	Stabilizing	0.491	N	0.39	neutral	N	0.486889245	None	None	I
D/W	0.8481	likely_pathogenic	0.819	pathogenic	0.003	Stabilizing	0.991	D	0.395	neutral	None	None	None	None	I
D/Y	0.2238	likely_benign	0.2005	benign	0.068	Stabilizing	0.954	D	0.357	neutral	N	0.468801572	None	None	I

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.