TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21381	64366;64367;64368	chr2:178586760;178586759;178586758	chr2:179451487;179451486;179451485
N2AB	19740	59443;59444;59445	chr2:178586760;178586759;178586758	chr2:179451487;179451486;179451485
N2A	18813	56662;56663;56664	chr2:178586760;178586759;178586758	chr2:179451487;179451486;179451485
N2B	12316	37171;37172;37173	chr2:178586760;178586759;178586758	chr2:179451487;179451486;179451485
Novex-1	12441	37546;37547;37548	chr2:178586760;178586759;178586758	chr2:179451487;179451486;179451485
Novex-2	12508	37747;37748;37749	chr2:178586760;178586759;178586758	chr2:179451487;179451486;179451485
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-43
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.3463
• 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
N/S	rs2154181598	None	0.058	N	0.186	0.108	0.12205267543	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	1.94326E-04	None	0	0	0	0	0
N/S	rs2154181598	None	0.058	N	0.186	0.108	0.12205267543	gnomAD-4.0.0	6.57203E-06	None	None	None	None	N	None	0	0	None	0	1.9478E-04	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
N/A	0.4339	ambiguous	0.3781	ambiguous	-0.645	Destabilizing	0.754	D	0.425	neutral	None	None	None	None	N
N/C	0.4908	ambiguous	0.4439	ambiguous	0.23	Stabilizing	0.998	D	0.619	neutral	None	None	None	None	N
N/D	0.2032	likely_benign	0.1647	benign	-0.475	Destabilizing	0.822	D	0.461	neutral	N	0.469399563	None	None	N
N/E	0.5608	ambiguous	0.4435	ambiguous	-0.494	Destabilizing	0.86	D	0.403	neutral	None	None	None	None	N
N/F	0.6188	likely_pathogenic	0.5779	pathogenic	-0.97	Destabilizing	0.978	D	0.603	neutral	None	None	None	None	N
N/G	0.431	ambiguous	0.4074	ambiguous	-0.839	Destabilizing	0.754	D	0.376	neutral	None	None	None	None	N
N/H	0.1618	likely_benign	0.1487	benign	-0.914	Destabilizing	0.032	N	0.307	neutral	N	0.515211997	None	None	N
N/I	0.4958	ambiguous	0.4018	ambiguous	-0.208	Destabilizing	0.942	D	0.597	neutral	N	0.497528117	None	None	N
N/K	0.5559	ambiguous	0.4297	ambiguous	-0.01	Destabilizing	0.822	D	0.447	neutral	N	0.519001664	None	None	N
N/L	0.4358	ambiguous	0.3735	ambiguous	-0.208	Destabilizing	0.86	D	0.535	neutral	None	None	None	None	N
N/M	0.4422	ambiguous	0.3881	ambiguous	0.491	Stabilizing	0.998	D	0.563	neutral	None	None	None	None	N
N/P	0.9806	likely_pathogenic	0.973	pathogenic	-0.328	Destabilizing	0.978	D	0.556	neutral	None	None	None	None	N
N/Q	0.4887	ambiguous	0.4057	ambiguous	-0.697	Destabilizing	0.956	D	0.475	neutral	None	None	None	None	N
N/R	0.6169	likely_pathogenic	0.5106	ambiguous	0.132	Stabilizing	0.956	D	0.459	neutral	None	None	None	None	N
N/S	0.123	likely_benign	0.1185	benign	-0.361	Destabilizing	0.058	N	0.186	neutral	N	0.461086724	None	None	N
N/T	0.1363	likely_benign	0.1246	benign	-0.235	Destabilizing	0.058	N	0.205	neutral	N	0.453117814	None	None	N
N/V	0.4652	ambiguous	0.3802	ambiguous	-0.328	Destabilizing	0.956	D	0.533	neutral	None	None	None	None	N
N/W	0.8493	likely_pathogenic	0.8238	pathogenic	-0.835	Destabilizing	0.998	D	0.672	neutral	None	None	None	None	N
N/Y	0.2059	likely_benign	0.1797	benign	-0.59	Destabilizing	0.942	D	0.567	neutral	N	0.504276066	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.