TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26094	78505;78506;78507	chr2:178567852;178567851;178567850	chr2:179432579;179432578;179432577
N2AB	24453	73582;73583;73584	chr2:178567852;178567851;178567850	chr2:179432579;179432578;179432577
N2A	23526	70801;70802;70803	chr2:178567852;178567851;178567850	chr2:179432579;179432578;179432577
N2B	17029	51310;51311;51312	chr2:178567852;178567851;178567850	chr2:179432579;179432578;179432577
Novex-1	17154	51685;51686;51687	chr2:178567852;178567851;178567850	chr2:179432579;179432578;179432577
Novex-2	17221	51886;51887;51888	chr2:178567852;178567851;178567850	chr2:179432579;179432578;179432577
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-78
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.6361
• 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/N	None	None	0.351	N	0.193	0.067	0.16115917748	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
T/S	None	None	0.183	N	0.243	0.103	0.148003135375	gnomAD-4.0.0	1.5918E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85938E-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	0.0774	likely_benign	0.076	benign	-0.868	Destabilizing	0.047	N	0.16	neutral	N	0.454006036	None	None	N
T/C	0.2062	likely_benign	0.1813	benign	-0.574	Destabilizing	0.001	N	0.131	neutral	None	None	None	None	N
T/D	0.4502	ambiguous	0.43	ambiguous	-0.591	Destabilizing	0.418	N	0.277	neutral	None	None	None	None	N
T/E	0.2654	likely_benign	0.2569	benign	-0.627	Destabilizing	0.129	N	0.289	neutral	None	None	None	None	N
T/F	0.2026	likely_benign	0.1963	benign	-1.212	Destabilizing	0.836	D	0.334	neutral	None	None	None	None	N
T/G	0.2807	likely_benign	0.2934	benign	-1.062	Destabilizing	0.228	N	0.277	neutral	None	None	None	None	N
T/H	0.1698	likely_benign	0.1682	benign	-1.45	Destabilizing	0.836	D	0.304	neutral	None	None	None	None	N
T/I	0.1016	likely_benign	0.0997	benign	-0.45	Destabilizing	0.351	N	0.377	neutral	N	0.519614952	None	None	N
T/K	0.0861	likely_benign	0.0838	benign	-0.739	Destabilizing	0.129	N	0.297	neutral	None	None	None	None	N
T/L	0.074	likely_benign	0.0732	benign	-0.45	Destabilizing	0.129	N	0.293	neutral	None	None	None	None	N
T/M	0.0771	likely_benign	0.0767	benign	0.028	Stabilizing	0.94	D	0.319	neutral	None	None	None	None	N
T/N	0.1092	likely_benign	0.1114	benign	-0.654	Destabilizing	0.351	N	0.193	neutral	N	0.437492214	None	None	N
T/P	0.0983	likely_benign	0.1044	benign	-0.56	Destabilizing	0.77	D	0.375	neutral	N	0.462414875	None	None	N
T/Q	0.1214	likely_benign	0.1268	benign	-0.968	Destabilizing	0.012	N	0.115	neutral	None	None	None	None	N
T/R	0.0783	likely_benign	0.0839	benign	-0.407	Destabilizing	0.001	N	0.109	neutral	None	None	None	None	N
T/S	0.1231	likely_benign	0.1213	benign	-0.874	Destabilizing	0.183	N	0.243	neutral	N	0.472842513	None	None	N
T/V	0.0917	likely_benign	0.0928	benign	-0.56	Destabilizing	0.129	N	0.174	neutral	None	None	None	None	N
T/W	0.5413	ambiguous	0.5286	ambiguous	-1.115	Destabilizing	0.983	D	0.293	neutral	None	None	None	None	N
T/Y	0.2158	likely_benign	0.2014	benign	-0.868	Destabilizing	0.94	D	0.378	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.