TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14916	44971;44972;44973	chr2:178624534;178624533;178624532	chr2:179489261;179489260;179489259
N2AB	13275	40048;40049;40050	chr2:178624534;178624533;178624532	chr2:179489261;179489260;179489259
N2A	12348	37267;37268;37269	chr2:178624534;178624533;178624532	chr2:179489261;179489260;179489259
N2B	5851	17776;17777;17778	chr2:178624534;178624533;178624532	chr2:179489261;179489260;179489259
Novex-1	5976	18151;18152;18153	chr2:178624534;178624533;178624532	chr2:179489261;179489260;179489259
Novex-2	6043	18352;18353;18354	chr2:178624534;178624533;178624532	chr2:179489261;179489260;179489259
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-100
• Domain position: 64
• Structural Position: 146
• Q(SASA): 0.6265
• 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
P/L	None	None	0.002	N	0.236	0.138	0.261217442401	gnomAD-4.0.0	1.20033E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
P/S	rs2058747129	None	0.891	N	0.309	0.182	0.117506650769	gnomAD-4.0.0	3.18692E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	5.72485E-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
P/A	0.0731	likely_benign	0.0779	benign	-0.76	Destabilizing	0.625	D	0.282	neutral	N	0.346510809	None	None	N
P/C	0.6402	likely_pathogenic	0.6589	pathogenic	-0.615	Destabilizing	0.998	D	0.367	neutral	None	None	None	None	N
P/D	0.3582	ambiguous	0.4516	ambiguous	-0.737	Destabilizing	0.991	D	0.277	neutral	None	None	None	None	N
P/E	0.2023	likely_benign	0.2446	benign	-0.844	Destabilizing	0.974	D	0.278	neutral	None	None	None	None	N
P/F	0.5061	ambiguous	0.4799	ambiguous	-0.895	Destabilizing	0.949	D	0.385	neutral	None	None	None	None	N
P/G	0.2785	likely_benign	0.3427	ambiguous	-0.925	Destabilizing	0.915	D	0.343	neutral	None	None	None	None	N
P/H	0.2075	likely_benign	0.2072	benign	-0.462	Destabilizing	0.998	D	0.345	neutral	None	None	None	None	N
P/I	0.263	likely_benign	0.2345	benign	-0.462	Destabilizing	0.728	D	0.357	neutral	None	None	None	None	N
P/K	0.1979	likely_benign	0.2494	benign	-0.724	Destabilizing	0.915	D	0.29	neutral	None	None	None	None	N
P/L	0.1007	likely_benign	0.0792	benign	-0.462	Destabilizing	0.002	N	0.236	neutral	N	0.343232486	None	None	N
P/M	0.2675	likely_benign	0.2437	benign	-0.395	Destabilizing	0.325	N	0.285	neutral	None	None	None	None	N
P/N	0.3023	likely_benign	0.3519	ambiguous	-0.397	Destabilizing	0.991	D	0.359	neutral	None	None	None	None	N
P/Q	0.1354	likely_benign	0.1469	benign	-0.679	Destabilizing	0.966	D	0.273	neutral	N	0.342038696	None	None	N
P/R	0.1448	likely_benign	0.1602	benign	-0.108	Destabilizing	0.966	D	0.361	neutral	N	0.338262325	None	None	N
P/S	0.1177	likely_benign	0.1291	benign	-0.737	Destabilizing	0.891	D	0.309	neutral	N	0.350937601	None	None	N
P/T	0.104	likely_benign	0.098	benign	-0.749	Destabilizing	0.801	D	0.297	neutral	N	0.342140622	None	None	N
P/V	0.1794	likely_benign	0.1692	benign	-0.527	Destabilizing	0.525	D	0.287	neutral	None	None	None	None	N
P/W	0.6411	likely_pathogenic	0.6228	pathogenic	-0.973	Destabilizing	0.998	D	0.402	neutral	None	None	None	None	N
P/Y	0.4642	ambiguous	0.4663	ambiguous	-0.698	Destabilizing	0.974	D	0.371	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.