TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23410	70453;70454;70455	chr2:178575904;178575903;178575902	chr2:179440631;179440630;179440629
N2AB	21769	65530;65531;65532	chr2:178575904;178575903;178575902	chr2:179440631;179440630;179440629
N2A	20842	62749;62750;62751	chr2:178575904;178575903;178575902	chr2:179440631;179440630;179440629
N2B	14345	43258;43259;43260	chr2:178575904;178575903;178575902	chr2:179440631;179440630;179440629
Novex-1	14470	43633;43634;43635	chr2:178575904;178575903;178575902	chr2:179440631;179440630;179440629
Novex-2	14537	43834;43835;43836	chr2:178575904;178575903;178575902	chr2:179440631;179440630;179440629
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: Ig-129
• Domain position: 66
• Structural Position: 151
• Q(SASA): 0.2921
• 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
T/N	rs1473979874	-0.468	0.491	N	0.437	0.334	0.337868961071	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
T/N	rs1473979874	-0.468	0.491	N	0.437	0.334	0.337868961071	gnomAD-4.0.0	1.36855E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79914E-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	0.06	likely_benign	0.0803	benign	-0.876	Destabilizing	None	N	0.149	neutral	N	0.378828778	None	None	I
T/C	0.3904	ambiguous	0.4745	ambiguous	-0.499	Destabilizing	0.901	D	0.521	neutral	None	None	None	None	I
T/D	0.7739	likely_pathogenic	0.832	pathogenic	0.234	Stabilizing	0.561	D	0.501	neutral	None	None	None	None	I
T/E	0.6877	likely_pathogenic	0.741	pathogenic	0.231	Stabilizing	0.561	D	0.521	neutral	None	None	None	None	I
T/F	0.5684	likely_pathogenic	0.7215	pathogenic	-1.038	Destabilizing	0.818	D	0.561	neutral	None	None	None	None	I
T/G	0.1869	likely_benign	0.2358	benign	-1.113	Destabilizing	0.209	N	0.387	neutral	None	None	None	None	I
T/H	0.4995	ambiguous	0.5782	pathogenic	-1.364	Destabilizing	0.965	D	0.519	neutral	None	None	None	None	I
T/I	0.5759	likely_pathogenic	0.6875	pathogenic	-0.338	Destabilizing	0.003	N	0.248	neutral	D	0.53227011	None	None	I
T/K	0.5647	likely_pathogenic	0.6517	pathogenic	-0.512	Destabilizing	0.561	D	0.52	neutral	None	None	None	None	I
T/L	0.242	likely_benign	0.3371	benign	-0.338	Destabilizing	0.083	N	0.341	neutral	None	None	None	None	I
T/M	0.1341	likely_benign	0.1715	benign	-0.054	Destabilizing	0.818	D	0.536	neutral	None	None	None	None	I
T/N	0.2426	likely_benign	0.2973	benign	-0.445	Destabilizing	0.491	N	0.437	neutral	N	0.494135797	None	None	I
T/P	0.6856	likely_pathogenic	0.7785	pathogenic	-0.486	Destabilizing	0.662	D	0.524	neutral	D	0.53227011	None	None	I
T/Q	0.4419	ambiguous	0.5033	ambiguous	-0.606	Destabilizing	0.901	D	0.561	neutral	None	None	None	None	I
T/R	0.4405	ambiguous	0.549	ambiguous	-0.333	Destabilizing	0.722	D	0.542	neutral	None	None	None	None	I
T/S	0.0976	likely_benign	0.117	benign	-0.817	Destabilizing	0.016	N	0.173	neutral	N	0.383791881	None	None	I
T/V	0.3538	ambiguous	0.4556	ambiguous	-0.486	Destabilizing	0.038	N	0.311	neutral	None	None	None	None	I
T/W	0.8823	likely_pathogenic	0.931	pathogenic	-0.931	Destabilizing	0.991	D	0.539	neutral	None	None	None	None	I
T/Y	0.5608	ambiguous	0.6789	pathogenic	-0.692	Destabilizing	0.901	D	0.531	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.