TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20237	60934;60935;60936	chr2:178591016;178591015;178591014	chr2:179455743;179455742;179455741
N2AB	18596	56011;56012;56013	chr2:178591016;178591015;178591014	chr2:179455743;179455742;179455741
N2A	17669	53230;53231;53232	chr2:178591016;178591015;178591014	chr2:179455743;179455742;179455741
N2B	11172	33739;33740;33741	chr2:178591016;178591015;178591014	chr2:179455743;179455742;179455741
Novex-1	11297	34114;34115;34116	chr2:178591016;178591015;178591014	chr2:179455743;179455742;179455741
Novex-2	11364	34315;34316;34317	chr2:178591016;178591015;178591014	chr2:179455743;179455742;179455741
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Q
• RefSeq wild type transcript codon: CAG
• RefSeq wild type template codon: GTC
• Domain: Fn3-34
• Domain position: 67
• Structural Position: 98
• Q(SASA): 0.7177
• 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
Q/R	None	None	0.549	N	0.447	0.166	0.148003135375	gnomAD-4.0.0	1.5919E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85977E-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
Q/A	0.333	likely_benign	0.3115	benign	-0.442	Destabilizing	0.4	N	0.421	neutral	None	None	None	None	N
Q/C	0.7484	likely_pathogenic	0.6951	pathogenic	0.04	Stabilizing	0.992	D	0.435	neutral	None	None	None	None	N
Q/D	0.6354	likely_pathogenic	0.6273	pathogenic	0.122	Stabilizing	0.617	D	0.414	neutral	None	None	None	None	N
Q/E	0.0982	likely_benign	0.1049	benign	0.139	Stabilizing	0.334	N	0.391	neutral	N	0.423317769	None	None	N
Q/F	0.7916	likely_pathogenic	0.763	pathogenic	-0.504	Destabilizing	0.85	D	0.426	neutral	None	None	None	None	N
Q/G	0.4288	ambiguous	0.4262	ambiguous	-0.679	Destabilizing	0.617	D	0.454	neutral	None	None	None	None	N
Q/H	0.3289	likely_benign	0.295	benign	-0.401	Destabilizing	0.009	N	0.245	neutral	N	0.467303407	None	None	N
Q/I	0.3854	ambiguous	0.3525	ambiguous	0.11	Stabilizing	0.447	N	0.411	neutral	None	None	None	None	N
Q/K	0.1153	likely_benign	0.1118	benign	0.023	Stabilizing	0.549	D	0.411	neutral	N	0.445405195	None	None	N
Q/L	0.1534	likely_benign	0.1396	benign	0.11	Stabilizing	0.379	N	0.428	neutral	N	0.467706052	None	None	N
Q/M	0.4123	ambiguous	0.3688	ambiguous	0.318	Stabilizing	0.92	D	0.389	neutral	None	None	None	None	N
Q/N	0.4788	ambiguous	0.4574	ambiguous	-0.433	Destabilizing	0.447	N	0.399	neutral	None	None	None	None	N
Q/P	0.4005	ambiguous	0.4171	ambiguous	-0.044	Destabilizing	0.963	D	0.409	neutral	N	0.47214248	None	None	N
Q/R	0.1255	likely_benign	0.1227	benign	0.185	Stabilizing	0.549	D	0.447	neutral	N	0.47682418	None	None	N
Q/S	0.3968	ambiguous	0.3753	ambiguous	-0.481	Destabilizing	0.617	D	0.377	neutral	None	None	None	None	N
Q/T	0.2802	likely_benign	0.2628	benign	-0.283	Destabilizing	0.617	D	0.445	neutral	None	None	None	None	N
Q/V	0.2407	likely_benign	0.2153	benign	-0.044	Destabilizing	0.021	N	0.287	neutral	None	None	None	None	N
Q/W	0.6466	likely_pathogenic	0.6384	pathogenic	-0.42	Destabilizing	0.992	D	0.477	neutral	None	None	None	None	N
Q/Y	0.6067	likely_pathogenic	0.5691	pathogenic	-0.183	Destabilizing	0.739	D	0.405	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.