TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17235	51928;51929;51930	chr2:178609720;178609719;178609718	chr2:179474447;179474446;179474445
N2AB	15594	47005;47006;47007	chr2:178609720;178609719;178609718	chr2:179474447;179474446;179474445
N2A	14667	44224;44225;44226	chr2:178609720;178609719;178609718	chr2:179474447;179474446;179474445
N2B	8170	24733;24734;24735	chr2:178609720;178609719;178609718	chr2:179474447;179474446;179474445
Novex-1	8295	25108;25109;25110	chr2:178609720;178609719;178609718	chr2:179474447;179474446;179474445
Novex-2	8362	25309;25310;25311	chr2:178609720;178609719;178609718	chr2:179474447;179474446;179474445
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: Fn3-13
• Domain position: 89
• Structural Position: 122
• Q(SASA): 0.5096
• Predicted PPI site: I

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/P	None	None	0.969	N	0.517	0.195	0.308904156042	gnomAD-4.0.0	5.49811E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.22408E-06	0	0
R/Q	rs573695008	0.17	0.76	N	0.515	0.096	0.139678290688	gnomAD-2.1.1	1.52042E-04	None	None	None	None	I	None	0	6.54264E-04	None	0	9.28409E-04	None	3.35E-05	None	0	0	0
R/Q	rs573695008	0.17	0.76	N	0.515	0.096	0.139678290688	gnomAD-3.1.2	6.59E-05	None	None	None	None	I	None	2.42E-05	6.57E-05	0	0	9.74279E-04	None	0	0	1.47E-05	2.07383E-04	4.78927E-04
R/Q	rs573695008	0.17	0.76	N	0.515	0.096	0.139678290688	1000 genomes	1.99681E-04	None	None	None	None	I	None	0	0	None	None	0	0	None	None	None	1E-03	None
R/Q	rs573695008	0.17	0.76	N	0.515	0.096	0.139678290688	gnomAD-4.0.0	4.54258E-05	None	None	None	None	I	None	1.33636E-05	5.01538E-04	None	0	6.04216E-04	None	0	0	5.95577E-06	5.54004E-05	4.82393E-05
R/W	rs373860372	-0.355	0.996	N	0.611	0.272	None	gnomAD-2.1.1	1.22E-05	None	None	None	None	I	None	6.48E-05	0	None	0	0	None	0	None	0	1.8E-05	0
R/W	rs373860372	-0.355	0.996	N	0.611	0.272	None	gnomAD-3.1.2	6.58E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
R/W	rs373860372	-0.355	0.996	N	0.611	0.272	None	gnomAD-4.0.0	9.9522E-06	None	None	None	None	I	None	0	0	None	3.40832E-05	4.47467E-05	None	0	0	1.10576E-05	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
R/A	0.6844	likely_pathogenic	0.4651	ambiguous	-0.123	Destabilizing	0.428	N	0.365	neutral	None	None	None	None	I
R/C	0.5416	ambiguous	0.3091	benign	-0.431	Destabilizing	0.984	D	0.548	neutral	None	None	None	None	I
R/D	0.8669	likely_pathogenic	0.7357	pathogenic	-0.393	Destabilizing	0.272	N	0.445	neutral	None	None	None	None	I
R/E	0.6337	likely_pathogenic	0.4468	ambiguous	-0.375	Destabilizing	0.428	N	0.344	neutral	None	None	None	None	I
R/F	0.7755	likely_pathogenic	0.5937	pathogenic	-0.503	Destabilizing	0.842	D	0.495	neutral	None	None	None	None	I
R/G	0.6168	likely_pathogenic	0.3654	ambiguous	-0.21	Destabilizing	0.418	N	0.427	neutral	N	0.492444207	None	None	I
R/H	0.2617	likely_benign	0.1609	benign	-0.654	Destabilizing	0.005	N	0.393	neutral	None	None	None	None	I
R/I	0.5513	ambiguous	0.328	benign	0.057	Stabilizing	0.842	D	0.527	neutral	None	None	None	None	I
R/K	0.1801	likely_benign	0.127	benign	-0.392	Destabilizing	0.01	N	0.205	neutral	None	None	None	None	I
R/L	0.5126	ambiguous	0.3139	benign	0.057	Stabilizing	0.589	D	0.446	neutral	N	0.477514827	None	None	I
R/M	0.5904	likely_pathogenic	0.3637	ambiguous	-0.257	Destabilizing	0.984	D	0.423	neutral	None	None	None	None	I
R/N	0.8316	likely_pathogenic	0.6658	pathogenic	-0.325	Destabilizing	0.002	N	0.253	neutral	None	None	None	None	I
R/P	0.744	likely_pathogenic	0.5626	ambiguous	0.012	Stabilizing	0.969	D	0.517	neutral	N	0.448479999	None	None	I
R/Q	0.2399	likely_benign	0.181	benign	-0.339	Destabilizing	0.76	D	0.515	neutral	N	0.465430964	None	None	I
R/S	0.8031	likely_pathogenic	0.6002	pathogenic	-0.462	Destabilizing	0.272	N	0.389	neutral	None	None	None	None	I
R/T	0.6262	likely_pathogenic	0.3796	ambiguous	-0.366	Destabilizing	0.428	N	0.433	neutral	None	None	None	None	I
R/V	0.6227	likely_pathogenic	0.4241	ambiguous	0.012	Stabilizing	0.842	D	0.48	neutral	None	None	None	None	I
R/W	0.4399	ambiguous	0.26	benign	-0.727	Destabilizing	0.996	D	0.611	neutral	N	0.464919869	None	None	I
R/Y	0.6807	likely_pathogenic	0.4848	ambiguous	-0.357	Destabilizing	0.568	D	0.555	neutral	None	None	None	None	I

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.