TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21715	65368;65369;65370	chr2:178584408;178584407;178584406	chr2:179449135;179449134;179449133
N2AB	20074	60445;60446;60447	chr2:178584408;178584407;178584406	chr2:179449135;179449134;179449133
N2A	19147	57664;57665;57666	chr2:178584408;178584407;178584406	chr2:179449135;179449134;179449133
N2B	12650	38173;38174;38175	chr2:178584408;178584407;178584406	chr2:179449135;179449134;179449133
Novex-1	12775	38548;38549;38550	chr2:178584408;178584407;178584406	chr2:179449135;179449134;179449133
Novex-2	12842	38749;38750;38751	chr2:178584408;178584407;178584406	chr2:179449135;179449134;179449133
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: CGG
• RefSeq wild type template codon: GCC
• Domain: Fn3-45
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.6862
• 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
R/L	rs368450785	0.31	0.996	N	0.493	0.386	None	gnomAD-2.1.1	6.8E-05	None	None	None	None	N	None	4.14E-05	2.83E-05	None	0	0	None	0	None	0	1.25374E-04	1.40528E-04
R/L	rs368450785	0.31	0.996	N	0.493	0.386	None	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	7.25E-05	6.56E-05	0	0	0	None	0	0	5.88E-05	0	0
R/L	rs368450785	0.31	0.996	N	0.493	0.386	None	gnomAD-4.0.0	8.05896E-05	None	None	None	None	N	None	4.00844E-05	1.33458E-04	None	0	0	None	3.12471E-05	0	9.41074E-05	0	9.612E-05
R/Q	rs368450785	-0.033	0.999	N	0.554	0.292	0.207176502487	gnomAD-2.1.1	4.83E-05	None	None	None	None	N	None	0	0	None	0	0	None	1.9613E-04	None	0	3.57E-05	3.31785E-04
R/Q	rs368450785	-0.033	0.999	N	0.554	0.292	0.207176502487	gnomAD-3.1.2	3.29E-05	None	None	None	None	N	None	0	6.56E-05	0	0	0	None	0	0	1.47E-05	6.22148E-04	0
R/Q	rs368450785	-0.033	0.999	N	0.554	0.292	0.207176502487	gnomAD-4.0.0	4.02948E-05	None	None	None	None	N	None	1.33615E-05	1.66822E-05	None	0	0	None	0	0	3.6456E-05	1.86715E-04	4.806E-05
R/W	rs766522121	-0.413	1.0	N	0.678	0.425	0.398727352345	gnomAD-2.1.1	2.15E-05	None	None	None	None	N	None	4.13E-05	0	None	9.69E-05	1.54623E-04	None	3.27E-05	None	0	0	0
R/W	rs766522121	-0.413	1.0	N	0.678	0.425	0.398727352345	gnomAD-3.1.2	5.26E-05	None	None	None	None	N	None	1.68968E-04	0	0	0	0	None	0	0	1.47E-05	0	0
R/W	rs766522121	-0.413	1.0	N	0.678	0.425	0.398727352345	gnomAD-4.0.0	2.47961E-05	None	None	None	None	N	None	1.46929E-04	0	None	3.37998E-05	1.11692E-04	None	0	0	1.3565E-05	4.393E-05	4.80538E-05

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
R/A	0.5521	ambiguous	0.3783	ambiguous	-0.017	Destabilizing	0.985	D	0.512	neutral	None	None	None	None	N
R/C	0.277	likely_benign	0.185	benign	-0.297	Destabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	N
R/D	0.7787	likely_pathogenic	0.626	pathogenic	-0.127	Destabilizing	0.998	D	0.533	neutral	None	None	None	None	N
R/E	0.5867	likely_pathogenic	0.4356	ambiguous	-0.078	Destabilizing	0.985	D	0.525	neutral	None	None	None	None	N
R/F	0.7175	likely_pathogenic	0.5691	pathogenic	-0.306	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
R/G	0.3823	ambiguous	0.2498	benign	-0.175	Destabilizing	0.996	D	0.493	neutral	N	0.490062836	None	None	N
R/H	0.1492	likely_benign	0.1103	benign	-0.561	Destabilizing	0.999	D	0.571	neutral	None	None	None	None	N
R/I	0.4946	ambiguous	0.3765	ambiguous	0.353	Stabilizing	0.999	D	0.65	neutral	None	None	None	None	N
R/K	0.1467	likely_benign	0.1202	benign	-0.139	Destabilizing	0.271	N	0.228	neutral	None	None	None	None	N
R/L	0.3669	ambiguous	0.2565	benign	0.353	Stabilizing	0.996	D	0.493	neutral	N	0.504360285	None	None	N
R/M	0.4775	ambiguous	0.3564	ambiguous	-0.069	Destabilizing	1.0	D	0.578	neutral	None	None	None	None	N
R/N	0.6738	likely_pathogenic	0.5218	ambiguous	-0.019	Destabilizing	0.998	D	0.531	neutral	None	None	None	None	N
R/P	0.478	ambiguous	0.2857	benign	0.248	Stabilizing	1.0	D	0.637	neutral	N	0.464071101	None	None	N
R/Q	0.1648	likely_benign	0.1218	benign	-0.093	Destabilizing	0.999	D	0.554	neutral	N	0.493836647	None	None	N
R/S	0.6106	likely_pathogenic	0.4407	ambiguous	-0.318	Destabilizing	0.985	D	0.534	neutral	None	None	None	None	N
R/T	0.3755	ambiguous	0.2646	benign	-0.152	Destabilizing	0.993	D	0.512	neutral	None	None	None	None	N
R/V	0.5475	ambiguous	0.4007	ambiguous	0.248	Stabilizing	0.998	D	0.623	neutral	None	None	None	None	N
R/W	0.3083	likely_benign	0.2179	benign	-0.418	Destabilizing	1.0	D	0.678	prob.neutral	N	0.496896233	None	None	N
R/Y	0.5416	ambiguous	0.3987	ambiguous	-0.007	Destabilizing	0.999	D	0.64	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.