TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31400	94423;94424;94425	chr2:178547428;178547427;178547426	chr2:179412155;179412154;179412153
N2AB	29759	89500;89501;89502	chr2:178547428;178547427;178547426	chr2:179412155;179412154;179412153
N2A	28832	86719;86720;86721	chr2:178547428;178547427;178547426	chr2:179412155;179412154;179412153
N2B	22335	67228;67229;67230	chr2:178547428;178547427;178547426	chr2:179412155;179412154;179412153
Novex-1	22460	67603;67604;67605	chr2:178547428;178547427;178547426	chr2:179412155;179412154;179412153
Novex-2	22527	67804;67805;67806	chr2:178547428;178547427;178547426	chr2:179412155;179412154;179412153
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATA
• RefSeq wild type template codon: TAT
• Domain: Fn3-116
• Domain position: 93
• Structural Position: 127
• Q(SASA): 0.18
• 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
I/T	rs1261202731	None	0.321	N	0.742	0.307	0.617248042353	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
I/T	rs1261202731	None	0.321	N	0.742	0.307	0.617248042353	gnomAD-4.0.0	6.57082E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.47003E-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
I/A	0.5698	likely_pathogenic	0.6205	pathogenic	-2.177	Highly Destabilizing	0.239	N	0.63	neutral	None	None	None	None	N
I/C	0.6897	likely_pathogenic	0.7071	pathogenic	-1.402	Destabilizing	0.944	D	0.707	prob.delet.	None	None	None	None	N
I/D	0.9705	likely_pathogenic	0.976	pathogenic	-1.9	Destabilizing	0.817	D	0.83	deleterious	None	None	None	None	N
I/E	0.8995	likely_pathogenic	0.9165	pathogenic	-1.728	Destabilizing	0.817	D	0.791	deleterious	None	None	None	None	N
I/F	0.2406	likely_benign	0.2725	benign	-1.226	Destabilizing	0.687	D	0.648	neutral	None	None	None	None	N
I/G	0.8938	likely_pathogenic	0.9084	pathogenic	-2.661	Highly Destabilizing	0.817	D	0.771	deleterious	None	None	None	None	N
I/H	0.8563	likely_pathogenic	0.8741	pathogenic	-1.783	Destabilizing	0.981	D	0.823	deleterious	None	None	None	None	N
I/K	0.7677	likely_pathogenic	0.8197	pathogenic	-1.635	Destabilizing	0.771	D	0.806	deleterious	N	0.490243054	None	None	N
I/L	0.1393	likely_benign	0.1443	benign	-0.821	Destabilizing	0.041	N	0.428	neutral	N	0.511742044	None	None	N
I/M	0.1286	likely_benign	0.134	benign	-0.718	Destabilizing	0.624	D	0.619	neutral	N	0.481384638	None	None	N
I/N	0.8263	likely_pathogenic	0.8454	pathogenic	-1.808	Destabilizing	0.931	D	0.816	deleterious	None	None	None	None	N
I/P	0.9798	likely_pathogenic	0.9851	pathogenic	-1.249	Destabilizing	0.931	D	0.826	deleterious	None	None	None	None	N
I/Q	0.7872	likely_pathogenic	0.8093	pathogenic	-1.753	Destabilizing	0.931	D	0.804	deleterious	None	None	None	None	N
I/R	0.7161	likely_pathogenic	0.778	pathogenic	-1.245	Destabilizing	0.771	D	0.821	deleterious	N	0.490243054	None	None	N
I/S	0.7393	likely_pathogenic	0.7597	pathogenic	-2.531	Highly Destabilizing	0.687	D	0.661	prob.neutral	None	None	None	None	N
I/T	0.4949	ambiguous	0.5122	ambiguous	-2.213	Highly Destabilizing	0.321	N	0.742	deleterious	N	0.461970581	None	None	N
I/V	0.0548	likely_benign	0.0548	benign	-1.249	Destabilizing	0.001	N	0.207	neutral	N	0.421197397	None	None	N
I/W	0.9253	likely_pathogenic	0.9392	pathogenic	-1.442	Destabilizing	0.981	D	0.766	deleterious	None	None	None	None	N
I/Y	0.7606	likely_pathogenic	0.8038	pathogenic	-1.175	Destabilizing	0.817	D	0.717	prob.delet.	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.