TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14261	43006;43007;43008	chr2:178633578;178633577;178633576	chr2:179498305;179498304;179498303
N2AB	12620	38083;38084;38085	chr2:178633578;178633577;178633576	chr2:179498305;179498304;179498303
N2A	11693	35302;35303;35304	chr2:178633578;178633577;178633576	chr2:179498305;179498304;179498303
N2B	5196	15811;15812;15813	chr2:178633578;178633577;178633576	chr2:179498305;179498304;179498303
Novex-1	5321	16186;16187;16188	chr2:178633578;178633577;178633576	chr2:179498305;179498304;179498303
Novex-2	5388	16387;16388;16389	chr2:178633578;178633577;178633576	chr2:179498305;179498304;179498303
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-93
• Domain position: 31
• Structural Position: 47
• Q(SASA): 0.6548
• 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
K/R	None	None	0.99	N	0.628	0.266	0.473774312618	gnomAD-4.0.0	1.5923E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85959E-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
K/A	0.427	ambiguous	0.3428	ambiguous	-0.701	Destabilizing	0.985	D	0.681	prob.neutral	None	None	None	None	N
K/C	0.6841	likely_pathogenic	0.6269	pathogenic	-0.608	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
K/D	0.7477	likely_pathogenic	0.6739	pathogenic	-0.139	Destabilizing	0.999	D	0.663	neutral	None	None	None	None	N
K/E	0.2779	likely_benign	0.2173	benign	-0.004	Destabilizing	0.997	D	0.651	neutral	N	0.506167461	None	None	N
K/F	0.8076	likely_pathogenic	0.7101	pathogenic	-0.263	Destabilizing	0.996	D	0.691	prob.neutral	None	None	None	None	N
K/G	0.5994	likely_pathogenic	0.513	ambiguous	-1.089	Destabilizing	0.998	D	0.653	neutral	None	None	None	None	N
K/H	0.2826	likely_benign	0.2679	benign	-1.328	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	N
K/I	0.3355	likely_benign	0.2453	benign	0.314	Stabilizing	0.961	D	0.648	neutral	N	0.512215485	None	None	N
K/L	0.3504	ambiguous	0.2808	benign	0.314	Stabilizing	0.931	D	0.641	neutral	None	None	None	None	N
K/M	0.2483	likely_benign	0.1914	benign	0.122	Stabilizing	0.856	D	0.406	neutral	None	None	None	None	N
K/N	0.4226	ambiguous	0.3373	benign	-0.559	Destabilizing	0.999	D	0.629	neutral	D	0.585565537	None	None	N
K/P	0.9519	likely_pathogenic	0.9346	pathogenic	0.005	Stabilizing	0.999	D	0.668	neutral	None	None	None	None	N
K/Q	0.1422	likely_benign	0.1257	benign	-0.555	Destabilizing	0.997	D	0.653	neutral	N	0.512093164	None	None	N
K/R	0.0977	likely_benign	0.0922	benign	-0.655	Destabilizing	0.99	D	0.628	neutral	N	0.511086878	None	None	N
K/S	0.4248	ambiguous	0.3485	ambiguous	-1.215	Destabilizing	0.993	D	0.633	neutral	None	None	None	None	N
K/T	0.1574	likely_benign	0.1311	benign	-0.863	Destabilizing	0.98	D	0.643	neutral	N	0.504892292	None	None	N
K/V	0.2977	likely_benign	0.2376	benign	0.005	Stabilizing	0.469	N	0.471	neutral	None	None	None	None	N
K/W	0.8306	likely_pathogenic	0.7814	pathogenic	-0.143	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	N
K/Y	0.6958	likely_pathogenic	0.598	pathogenic	0.117	Stabilizing	0.999	D	0.686	prob.neutral	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.