TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33264	100015;100016;100017	chr2:178537417;178537416;178537415	chr2:179402144;179402143;179402142
N2AB	31623	95092;95093;95094	chr2:178537417;178537416;178537415	chr2:179402144;179402143;179402142
N2A	30696	92311;92312;92313	chr2:178537417;178537416;178537415	chr2:179402144;179402143;179402142
N2B	24199	72820;72821;72822	chr2:178537417;178537416;178537415	chr2:179402144;179402143;179402142
Novex-1	24324	73195;73196;73197	chr2:178537417;178537416;178537415	chr2:179402144;179402143;179402142
Novex-2	24391	73396;73397;73398	chr2:178537417;178537416;178537415	chr2:179402144;179402143;179402142
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-157
• Domain position: 62
• Structural Position: 149
• Q(SASA): 0.1837
• 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/Q	None	None	0.997	N	0.685	0.288	0.229924730088	gnomAD-4.0.0	1.59875E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43926E-05	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	0.7554	likely_pathogenic	0.7637	pathogenic	-1.159	Destabilizing	0.996	D	0.718	prob.delet.	None	None	None	None	N
H/C	0.4945	ambiguous	0.5463	ambiguous	-0.181	Destabilizing	1.0	D	0.806	deleterious	None	None	None	None	N
H/D	0.3249	likely_benign	0.289	benign	-1.259	Destabilizing	0.937	D	0.672	neutral	N	0.399352327	None	None	N
H/E	0.8023	likely_pathogenic	0.7616	pathogenic	-1.112	Destabilizing	0.982	D	0.605	neutral	None	None	None	None	N
H/F	0.6886	likely_pathogenic	0.7054	pathogenic	0.451	Stabilizing	0.999	D	0.773	deleterious	None	None	None	None	N
H/G	0.8387	likely_pathogenic	0.839	pathogenic	-1.576	Destabilizing	0.982	D	0.707	prob.neutral	None	None	None	None	N
H/I	0.8368	likely_pathogenic	0.8353	pathogenic	0.04	Stabilizing	0.999	D	0.827	deleterious	None	None	None	None	N
H/K	0.9138	likely_pathogenic	0.9041	pathogenic	-0.714	Destabilizing	0.981	D	0.705	prob.neutral	None	None	None	None	N
H/L	0.4308	ambiguous	0.4542	ambiguous	0.04	Stabilizing	0.988	D	0.796	deleterious	N	0.485528199	None	None	N
H/M	0.7435	likely_pathogenic	0.7461	pathogenic	-0.076	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
H/N	0.1309	likely_benign	0.1406	benign	-1.062	Destabilizing	0.143	N	0.327	neutral	N	0.492324856	None	None	N
H/P	0.8635	likely_pathogenic	0.8898	pathogenic	-0.344	Destabilizing	0.998	D	0.805	deleterious	N	0.485274709	None	None	N
H/Q	0.628	likely_pathogenic	0.5941	pathogenic	-0.731	Destabilizing	0.997	D	0.685	prob.neutral	N	0.511777408	None	None	N
H/R	0.8144	likely_pathogenic	0.8229	pathogenic	-1.31	Destabilizing	0.988	D	0.641	neutral	N	0.493615722	None	None	N
H/S	0.5343	ambiguous	0.5335	ambiguous	-1.008	Destabilizing	0.982	D	0.657	neutral	None	None	None	None	N
H/T	0.7849	likely_pathogenic	0.7759	pathogenic	-0.746	Destabilizing	0.975	D	0.753	deleterious	None	None	None	None	N
H/V	0.7695	likely_pathogenic	0.7772	pathogenic	-0.344	Destabilizing	0.999	D	0.815	deleterious	None	None	None	None	N
H/W	0.8233	likely_pathogenic	0.8369	pathogenic	0.819	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
H/Y	0.2992	likely_benign	0.3051	benign	0.746	Stabilizing	0.997	D	0.662	neutral	N	0.485274709	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.