TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22624	68095;68096;68097	chr2:178579160;178579159;178579158	chr2:179443887;179443886;179443885
N2AB	20983	63172;63173;63174	chr2:178579160;178579159;178579158	chr2:179443887;179443886;179443885
N2A	20056	60391;60392;60393	chr2:178579160;178579159;178579158	chr2:179443887;179443886;179443885
N2B	13559	40900;40901;40902	chr2:178579160;178579159;178579158	chr2:179443887;179443886;179443885
Novex-1	13684	41275;41276;41277	chr2:178579160;178579159;178579158	chr2:179443887;179443886;179443885
Novex-2	13751	41476;41477;41478	chr2:178579160;178579159;178579158	chr2:179443887;179443886;179443885
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Ig-127
• Domain position: 65
• Structural Position: 157
• Q(SASA): 0.206
• 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
T/I	None	None	0.007	N	0.513	0.29	0.317084106153	gnomAD-4.0.0	1.59209E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8599E-06	0	0
T/K	rs761798459	-0.637	0.213	N	0.654	0.3	0.3349148499	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
T/K	rs761798459	-0.637	0.213	N	0.654	0.3	0.3349148499	gnomAD-4.0.0	1.59209E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8599E-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
T/A	0.1207	likely_benign	0.1079	benign	-1.063	Destabilizing	0.101	N	0.465	neutral	N	0.490340819	None	None	N
T/C	0.3385	likely_benign	0.3308	benign	-0.875	Destabilizing	0.983	D	0.655	neutral	None	None	None	None	N
T/D	0.7009	likely_pathogenic	0.613	pathogenic	-0.892	Destabilizing	0.264	N	0.655	neutral	None	None	None	None	N
T/E	0.4791	ambiguous	0.4129	ambiguous	-0.817	Destabilizing	0.418	N	0.657	neutral	None	None	None	None	N
T/F	0.2383	likely_benign	0.2106	benign	-0.905	Destabilizing	0.836	D	0.739	prob.delet.	None	None	None	None	N
T/G	0.4186	ambiguous	0.366	ambiguous	-1.382	Destabilizing	0.264	N	0.677	prob.neutral	None	None	None	None	N
T/H	0.2836	likely_benign	0.2667	benign	-1.574	Destabilizing	0.005	N	0.595	neutral	None	None	None	None	N
T/I	0.1266	likely_benign	0.115	benign	-0.278	Destabilizing	0.007	N	0.513	neutral	N	0.485209669	None	None	N
T/K	0.3251	likely_benign	0.3126	benign	-0.821	Destabilizing	0.213	N	0.654	neutral	N	0.515375074	None	None	N
T/L	0.1039	likely_benign	0.0962	benign	-0.278	Destabilizing	0.129	N	0.613	neutral	None	None	None	None	N
T/M	0.092	likely_benign	0.0925	benign	-0.11	Destabilizing	0.836	D	0.683	prob.neutral	None	None	None	None	N
T/N	0.2268	likely_benign	0.1869	benign	-1.023	Destabilizing	0.01	N	0.406	neutral	None	None	None	None	N
T/P	0.8245	likely_pathogenic	0.8035	pathogenic	-0.507	Destabilizing	0.794	D	0.732	prob.delet.	N	0.521322316	None	None	N
T/Q	0.2886	likely_benign	0.273	benign	-1.115	Destabilizing	0.716	D	0.729	prob.delet.	None	None	None	None	N
T/R	0.2564	likely_benign	0.242	benign	-0.691	Destabilizing	0.655	D	0.714	prob.delet.	N	0.514068352	None	None	N
T/S	0.1458	likely_benign	0.1289	benign	-1.294	Destabilizing	0.007	N	0.267	neutral	N	0.50425679	None	None	N
T/V	0.1159	likely_benign	0.1122	benign	-0.507	Destabilizing	0.01	N	0.249	neutral	None	None	None	None	N
T/W	0.627	likely_pathogenic	0.5944	pathogenic	-0.858	Destabilizing	0.983	D	0.698	prob.neutral	None	None	None	None	N
T/Y	0.3225	likely_benign	0.2896	benign	-0.592	Destabilizing	0.716	D	0.747	deleterious	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.