TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7463	22612;22613;22614	chr2:178722400;178722399;178722398	chr2:179587127;179587126;179587125
N2AB	7146	21661;21662;21663	chr2:178722400;178722399;178722398	chr2:179587127;179587126;179587125
N2A	6219	18880;18881;18882	chr2:178722400;178722399;178722398	chr2:179587127;179587126;179587125
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: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-59
• Domain position: 45
• Structural Position: 102
• Q(SASA): 0.5658
• 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
E/G	None	None	0.101	N	0.255	0.196	0.448498829774	gnomAD-4.0.0	1.59199E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85987E-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
E/A	0.0914	likely_benign	0.104	benign	-0.003	Destabilizing	0.101	N	0.227	neutral	N	0.452740252	None	None	N
E/C	0.5836	likely_pathogenic	0.6439	pathogenic	-0.081	Destabilizing	0.983	D	0.283	neutral	None	None	None	None	N
E/D	0.0709	likely_benign	0.0849	benign	-0.227	Destabilizing	0.002	N	0.138	neutral	N	0.447043644	None	None	N
E/F	0.4798	ambiguous	0.5484	ambiguous	-0.097	Destabilizing	0.002	N	0.175	neutral	None	None	None	None	N
E/G	0.0779	likely_benign	0.0859	benign	-0.106	Destabilizing	0.101	N	0.255	neutral	N	0.445774207	None	None	N
E/H	0.1978	likely_benign	0.2479	benign	0.468	Stabilizing	0.005	N	0.106	neutral	None	None	None	None	N
E/I	0.2237	likely_benign	0.258	benign	0.21	Stabilizing	0.264	N	0.361	neutral	None	None	None	None	N
E/K	0.0758	likely_benign	0.0763	benign	0.456	Stabilizing	0.183	N	0.173	neutral	N	0.480676215	None	None	N
E/L	0.2489	likely_benign	0.2882	benign	0.21	Stabilizing	0.002	N	0.223	neutral	None	None	None	None	N
E/M	0.3055	likely_benign	0.3383	benign	0.048	Stabilizing	0.716	D	0.293	neutral	None	None	None	None	N
E/N	0.1072	likely_benign	0.1296	benign	0.297	Stabilizing	0.002	N	0.144	neutral	None	None	None	None	N
E/P	0.2398	likely_benign	0.2631	benign	0.157	Stabilizing	0.002	N	0.169	neutral	None	None	None	None	N
E/Q	0.0887	likely_benign	0.0993	benign	0.296	Stabilizing	0.351	N	0.249	neutral	N	0.473115524	None	None	N
E/R	0.1144	likely_benign	0.1214	benign	0.638	Stabilizing	0.418	N	0.225	neutral	None	None	None	None	N
E/S	0.0883	likely_benign	0.1112	benign	0.136	Stabilizing	0.027	N	0.165	neutral	None	None	None	None	N
E/T	0.1272	likely_benign	0.1448	benign	0.227	Stabilizing	0.129	N	0.278	neutral	None	None	None	None	N
E/V	0.1495	likely_benign	0.1676	benign	0.157	Stabilizing	0.007	N	0.158	neutral	N	0.510519119	None	None	N
E/W	0.6269	likely_pathogenic	0.6762	pathogenic	-0.071	Destabilizing	0.983	D	0.283	neutral	None	None	None	None	N
E/Y	0.3157	likely_benign	0.3789	ambiguous	0.123	Stabilizing	0.264	N	0.42	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.