TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4970	15133;15134;15135	chr2:178735538;178735537;178735536	chr2:179600265;179600264;179600263
N2AB	4653	14182;14183;14184	chr2:178735538;178735537;178735536	chr2:179600265;179600264;179600263
N2A	3726	11401;11402;11403	chr2:178735538;178735537;178735536	chr2:179600265;179600264;179600263
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-32
• Domain position: 83
• Structural Position: 168
• Q(SASA): 0.4266
• 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/F	rs1418301543	-1.202	0.971	D	0.739	0.374	0.777313054034	gnomAD-2.1.1	4.28E-06	None	None	None	None	N	None	0	0	None	0	5.85E-05	None	0	None	0	0	0
S/F	rs1418301543	-1.202	0.971	D	0.739	0.374	0.777313054034	gnomAD-3.1.2	1.31E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.94E-05	0	0
S/F	rs1418301543	-1.202	0.971	D	0.739	0.374	0.777313054034	gnomAD-4.0.0	1.31935E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.08441E-05	0	1.36091E-04

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	0.0869	likely_benign	0.0926	benign	-0.565	Destabilizing	0.489	N	0.41	neutral	N	0.513765347	None	None	N
S/C	0.1258	likely_benign	0.1251	benign	-0.281	Destabilizing	0.997	D	0.69	prob.neutral	D	0.584508556	None	None	N
S/D	0.3707	ambiguous	0.4319	ambiguous	0.482	Stabilizing	0.86	D	0.511	neutral	None	None	None	None	N
S/E	0.4531	ambiguous	0.4993	ambiguous	0.392	Stabilizing	0.86	D	0.517	neutral	None	None	None	None	N
S/F	0.128	likely_benign	0.1329	benign	-1.168	Destabilizing	0.971	D	0.739	prob.delet.	D	0.535318862	None	None	N
S/G	0.1199	likely_benign	0.1271	benign	-0.669	Destabilizing	0.86	D	0.469	neutral	None	None	None	None	N
S/H	0.2844	likely_benign	0.3057	benign	-1.108	Destabilizing	0.998	D	0.691	prob.neutral	None	None	None	None	N
S/I	0.138	likely_benign	0.145	benign	-0.415	Destabilizing	0.915	D	0.73	prob.delet.	None	None	None	None	N
S/K	0.5554	ambiguous	0.5919	pathogenic	-0.336	Destabilizing	0.86	D	0.516	neutral	None	None	None	None	N
S/L	0.0903	likely_benign	0.0918	benign	-0.415	Destabilizing	0.754	D	0.604	neutral	None	None	None	None	N
S/M	0.2064	likely_benign	0.2118	benign	-0.124	Destabilizing	0.994	D	0.695	prob.neutral	None	None	None	None	N
S/N	0.1523	likely_benign	0.1576	benign	-0.049	Destabilizing	0.86	D	0.513	neutral	None	None	None	None	N
S/P	0.4226	ambiguous	0.5052	ambiguous	-0.438	Destabilizing	0.971	D	0.743	deleterious	D	0.637013908	None	None	N
S/Q	0.4187	ambiguous	0.4491	ambiguous	-0.288	Destabilizing	0.978	D	0.605	neutral	None	None	None	None	N
S/R	0.4354	ambiguous	0.4624	ambiguous	-0.16	Destabilizing	0.956	D	0.738	prob.delet.	None	None	None	None	N
S/T	0.0771	likely_benign	0.0764	benign	-0.229	Destabilizing	0.006	N	0.237	neutral	N	0.393019727	None	None	N
S/V	0.1422	likely_benign	0.1524	benign	-0.438	Destabilizing	0.754	D	0.623	neutral	None	None	None	None	N
S/W	0.2863	likely_benign	0.3052	benign	-1.127	Destabilizing	0.998	D	0.665	neutral	None	None	None	None	N
S/Y	0.152	likely_benign	0.1559	benign	-0.858	Destabilizing	0.99	D	0.741	deleterious	N	0.513487162	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.