TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2840	8743;8744;8745	chr2:178770183;178770182;178770181	chr2:179634910;179634909;179634908
N2AB	2840	8743;8744;8745	chr2:178770183;178770182;178770181	chr2:179634910;179634909;179634908
N2A	2840	8743;8744;8745	chr2:178770183;178770182;178770181	chr2:179634910;179634909;179634908
N2B	2794	8605;8606;8607	chr2:178770183;178770182;178770181	chr2:179634910;179634909;179634908
Novex-1	2794	8605;8606;8607	chr2:178770183;178770182;178770181	chr2:179634910;179634909;179634908
Novex-2	2794	8605;8606;8607	chr2:178770183;178770182;178770181	chr2:179634910;179634909;179634908
Novex-3	2840	8743;8744;8745	chr2:178770183;178770182;178770181	chr2:179634910;179634909;179634908

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Ig-18
• Domain position: 46
• Structural Position: 121
• Q(SASA): 0.1917
• 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
H/R	None	None	0.784	N	0.477	0.373	0.253726318573	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
H/A	0.6583	likely_pathogenic	0.661	pathogenic	-1.441	Destabilizing	0.495	N	0.335	neutral	None	None	None	None	N
H/C	0.1781	likely_benign	0.1717	benign	-0.662	Destabilizing	0.003	N	0.335	neutral	None	None	None	None	N
H/D	0.7458	likely_pathogenic	0.7675	pathogenic	-1.316	Destabilizing	0.917	D	0.515	neutral	D	0.54045825	None	None	N
H/E	0.7054	likely_pathogenic	0.7153	pathogenic	-1.143	Destabilizing	0.828	D	0.425	neutral	None	None	None	None	N
H/F	0.2367	likely_benign	0.2527	benign	0.351	Stabilizing	0.543	D	0.495	neutral	None	None	None	None	N
H/G	0.7627	likely_pathogenic	0.7585	pathogenic	-1.875	Destabilizing	0.828	D	0.488	neutral	None	None	None	None	N
H/I	0.3634	ambiguous	0.3572	ambiguous	-0.18	Destabilizing	0.543	D	0.51	neutral	None	None	None	None	N
H/K	0.6436	likely_pathogenic	0.6447	pathogenic	-1.068	Destabilizing	0.828	D	0.47	neutral	None	None	None	None	N
H/L	0.2051	likely_benign	0.1929	benign	-0.18	Destabilizing	0.27	N	0.359	neutral	N	0.486991097	None	None	N
H/M	0.5908	likely_pathogenic	0.5903	pathogenic	-0.399	Destabilizing	0.944	D	0.507	neutral	None	None	None	None	N
H/N	0.2506	likely_benign	0.2802	benign	-1.509	Destabilizing	0.784	D	0.44	neutral	N	0.510762249	None	None	N
H/P	0.8611	likely_pathogenic	0.8196	pathogenic	-0.586	Destabilizing	0.975	D	0.559	neutral	N	0.510955798	None	None	N
H/Q	0.405	ambiguous	0.4275	ambiguous	-1.102	Destabilizing	0.975	D	0.489	neutral	N	0.510762249	None	None	N
H/R	0.3581	ambiguous	0.3573	ambiguous	-1.559	Destabilizing	0.784	D	0.477	neutral	N	0.510713645	None	None	N
H/S	0.5497	ambiguous	0.5741	pathogenic	-1.576	Destabilizing	0.828	D	0.52	neutral	None	None	None	None	N
H/T	0.527	ambiguous	0.5406	ambiguous	-1.283	Destabilizing	0.704	D	0.491	neutral	None	None	None	None	N
H/V	0.3037	likely_benign	0.2943	benign	-0.586	Destabilizing	0.013	N	0.353	neutral	None	None	None	None	N
H/W	0.4473	ambiguous	0.436	ambiguous	0.815	Stabilizing	0.985	D	0.494	neutral	None	None	None	None	N
H/Y	0.0621	likely_benign	0.0664	benign	0.708	Stabilizing	0.002	N	0.097	neutral	N	0.403218677	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.