TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4929	15010;15011;15012	chr2:178735661;178735660;178735659	chr2:179600388;179600387;179600386
N2AB	4612	14059;14060;14061	chr2:178735661;178735660;178735659	chr2:179600388;179600387;179600386
N2A	3685	11278;11279;11280	chr2:178735661;178735660;178735659	chr2:179600388;179600387;179600386
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: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-32
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.4635
• 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/A	rs2081317152	None	0.625	N	0.289	0.418	0.279370189704	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/A	rs2081317152	None	0.625	N	0.289	0.418	0.279370189704	gnomAD-4.0.0	6.57229E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47011E-05	0	0
P/S	None	None	0.891	N	0.273	0.417	0.286848849266	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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	0.069	likely_benign	0.0729	benign	-0.793	Destabilizing	0.625	D	0.289	neutral	N	0.409413464	None	None	N
P/C	0.2612	likely_benign	0.3453	ambiguous	-0.812	Destabilizing	0.998	D	0.422	neutral	None	None	None	None	N
P/D	0.3438	ambiguous	0.4644	ambiguous	-0.562	Destabilizing	0.915	D	0.324	neutral	None	None	None	None	N
P/E	0.2164	likely_benign	0.2912	benign	-0.576	Destabilizing	0.842	D	0.273	neutral	None	None	None	None	N
P/F	0.1517	likely_benign	0.198	benign	-0.664	Destabilizing	0.949	D	0.418	neutral	None	None	None	None	N
P/G	0.1908	likely_benign	0.2397	benign	-1.007	Destabilizing	0.915	D	0.324	neutral	None	None	None	None	N
P/H	0.1009	likely_benign	0.1229	benign	-0.306	Destabilizing	0.012	N	0.224	neutral	N	0.442620588	None	None	N
P/I	0.1035	likely_benign	0.127	benign	-0.321	Destabilizing	0.904	D	0.384	neutral	None	None	None	None	N
P/K	0.1895	likely_benign	0.2513	benign	-0.649	Destabilizing	0.728	D	0.295	neutral	None	None	None	None	N
P/L	0.0557	likely_benign	0.0607	benign	-0.321	Destabilizing	0.012	N	0.246	neutral	N	0.411414876	None	None	N
P/M	0.1382	likely_benign	0.1624	benign	-0.632	Destabilizing	0.949	D	0.375	neutral	None	None	None	None	N
P/N	0.1777	likely_benign	0.2371	benign	-0.591	Destabilizing	0.842	D	0.359	neutral	None	None	None	None	N
P/Q	0.092	likely_benign	0.1101	benign	-0.694	Destabilizing	0.949	D	0.333	neutral	None	None	None	None	N
P/R	0.1322	likely_benign	0.1688	benign	-0.222	Destabilizing	0.012	N	0.237	neutral	N	0.408187479	None	None	N
P/S	0.0815	likely_benign	0.0932	benign	-1.004	Destabilizing	0.891	D	0.273	neutral	N	0.356738818	None	None	N
P/T	0.0743	likely_benign	0.0826	benign	-0.902	Destabilizing	0.891	D	0.327	neutral	N	0.391615733	None	None	N
P/V	0.0915	likely_benign	0.1072	benign	-0.447	Destabilizing	0.728	D	0.339	neutral	None	None	None	None	N
P/W	0.2989	likely_benign	0.3918	ambiguous	-0.778	Destabilizing	0.998	D	0.473	neutral	None	None	None	None	N
P/Y	0.179	likely_benign	0.2352	benign	-0.486	Destabilizing	0.949	D	0.398	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.