TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21134	63625;63626;63627	chr2:178588007;178588006;178588005	chr2:179452734;179452733;179452732
N2AB	19493	58702;58703;58704	chr2:178588007;178588006;178588005	chr2:179452734;179452733;179452732
N2A	18566	55921;55922;55923	chr2:178588007;178588006;178588005	chr2:179452734;179452733;179452732
N2B	12069	36430;36431;36432	chr2:178588007;178588006;178588005	chr2:179452734;179452733;179452732
Novex-1	12194	36805;36806;36807	chr2:178588007;178588006;178588005	chr2:179452734;179452733;179452732
Novex-2	12261	37006;37007;37008	chr2:178588007;178588006;178588005	chr2:179452734;179452733;179452732
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Fn3-41
• Domain position: 71
• Structural Position: 96
• Q(SASA): 0.6375
• 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
S/I	None	None	0.996	N	0.423	0.32	0.430579932962	gnomAD-4.0.0	1.59341E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43361E-05	0
S/N	None	None	0.134	N	0.149	0.121	0.0611884634855	gnomAD-4.0.0	1.59341E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86139E-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
S/A	0.08	likely_benign	0.0806	benign	-0.163	Destabilizing	0.863	D	0.341	neutral	None	None	None	None	N
S/C	0.1316	likely_benign	0.1301	benign	-0.261	Destabilizing	0.999	D	0.415	neutral	N	0.463236531	None	None	N
S/D	0.2684	likely_benign	0.2582	benign	0.071	Stabilizing	0.759	D	0.306	neutral	None	None	None	None	N
S/E	0.434	ambiguous	0.4141	ambiguous	-0.032	Destabilizing	0.17	N	0.11	neutral	None	None	None	None	N
S/F	0.235	likely_benign	0.2416	benign	-0.861	Destabilizing	0.997	D	0.41	neutral	None	None	None	None	N
S/G	0.0792	likely_benign	0.0766	benign	-0.231	Destabilizing	0.826	D	0.306	neutral	N	0.334391197	None	None	N
S/H	0.3162	likely_benign	0.2927	benign	-0.559	Destabilizing	0.991	D	0.412	neutral	None	None	None	None	N
S/I	0.2659	likely_benign	0.2921	benign	-0.118	Destabilizing	0.996	D	0.423	neutral	N	0.505597144	None	None	N
S/K	0.6031	likely_pathogenic	0.5725	pathogenic	-0.359	Destabilizing	0.759	D	0.303	neutral	None	None	None	None	N
S/L	0.1227	likely_benign	0.1235	benign	-0.118	Destabilizing	0.939	D	0.349	neutral	None	None	None	None	N
S/M	0.2059	likely_benign	0.2105	benign	-0.089	Destabilizing	0.997	D	0.408	neutral	None	None	None	None	N
S/N	0.1215	likely_benign	0.1161	benign	-0.056	Destabilizing	0.134	N	0.149	neutral	N	0.366757119	None	None	N
S/P	0.3817	ambiguous	0.4076	ambiguous	-0.107	Destabilizing	0.997	D	0.427	neutral	None	None	None	None	N
S/Q	0.4571	ambiguous	0.4274	ambiguous	-0.288	Destabilizing	0.2	N	0.115	neutral	None	None	None	None	N
S/R	0.5811	likely_pathogenic	0.546	ambiguous	-0.091	Destabilizing	0.92	D	0.411	neutral	N	0.450954583	None	None	N
S/T	0.0992	likely_benign	0.1064	benign	-0.165	Destabilizing	0.826	D	0.318	neutral	N	0.491339768	None	None	N
S/V	0.2334	likely_benign	0.2456	benign	-0.107	Destabilizing	0.969	D	0.391	neutral	None	None	None	None	N
S/W	0.384	ambiguous	0.3901	ambiguous	-0.942	Destabilizing	0.999	D	0.502	neutral	None	None	None	None	N
S/Y	0.187	likely_benign	0.1902	benign	-0.624	Destabilizing	0.997	D	0.423	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.