TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5701	17326;17327;17328	chr2:178731774;178731773;178731772	chr2:179596501;179596500;179596499
N2AB	5384	16375;16376;16377	chr2:178731774;178731773;178731772	chr2:179596501;179596500;179596499
N2A	4457	13594;13595;13596	chr2:178731774;178731773;178731772	chr2:179596501;179596500;179596499
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-40
• Domain position: 65
• Structural Position: 146
• Q(SASA): 0.4953
• Predicted PPI site: I

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
A/D	rs757714302	-0.171	0.801	N	0.341	0.199	0.408714661073	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
A/D	rs757714302	-0.171	0.801	N	0.341	0.199	0.408714661073	gnomAD-4.0.0	1.36844E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79897E-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
A/C	0.508	ambiguous	0.4673	ambiguous	-0.741	Destabilizing	0.998	D	0.305	neutral	None	None	None	None	I
A/D	0.1996	likely_benign	0.1868	benign	-0.466	Destabilizing	0.801	D	0.341	neutral	N	0.508080089	None	None	I
A/E	0.2152	likely_benign	0.2054	benign	-0.549	Destabilizing	0.842	D	0.26	neutral	None	None	None	None	I
A/F	0.2539	likely_benign	0.2464	benign	-0.748	Destabilizing	0.974	D	0.365	neutral	None	None	None	None	I
A/G	0.1166	likely_benign	0.1153	benign	-0.563	Destabilizing	0.454	N	0.254	neutral	N	0.503770347	None	None	I
A/H	0.3899	ambiguous	0.375	ambiguous	-0.429	Destabilizing	0.037	N	0.297	neutral	None	None	None	None	I
A/I	0.1705	likely_benign	0.1566	benign	-0.226	Destabilizing	0.728	D	0.307	neutral	None	None	None	None	I
A/K	0.4115	ambiguous	0.3852	ambiguous	-0.732	Destabilizing	0.842	D	0.326	neutral	None	None	None	None	I
A/L	0.1282	likely_benign	0.1225	benign	-0.226	Destabilizing	0.728	D	0.268	neutral	None	None	None	None	I
A/M	0.167	likely_benign	0.1594	benign	-0.456	Destabilizing	0.974	D	0.285	neutral	None	None	None	None	I
A/N	0.1782	likely_benign	0.1715	benign	-0.495	Destabilizing	0.949	D	0.37	neutral	None	None	None	None	I
A/P	0.1039	likely_benign	0.0977	benign	-0.256	Destabilizing	0.012	N	0.198	neutral	N	0.424730774	None	None	I
A/Q	0.2939	likely_benign	0.2868	benign	-0.668	Destabilizing	0.974	D	0.321	neutral	None	None	None	None	I
A/R	0.3907	ambiguous	0.3815	ambiguous	-0.323	Destabilizing	0.949	D	0.31	neutral	None	None	None	None	I
A/S	0.0833	likely_benign	0.0828	benign	-0.766	Destabilizing	0.022	N	0.137	neutral	N	0.406377086	None	None	I
A/T	0.0785	likely_benign	0.0766	benign	-0.751	Destabilizing	0.669	D	0.24	neutral	N	0.472370005	None	None	I
A/V	0.0995	likely_benign	0.0951	benign	-0.256	Destabilizing	0.051	N	0.216	neutral	N	0.454437605	None	None	I
A/W	0.6313	likely_pathogenic	0.618	pathogenic	-0.961	Destabilizing	0.998	D	0.489	neutral	None	None	None	None	I
A/Y	0.3818	ambiguous	0.3565	ambiguous	-0.583	Destabilizing	0.949	D	0.381	neutral	None	None	None	None	I

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.