TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24337	73234;73235;73236	chr2:178573123;178573122;178573121	chr2:179437850;179437849;179437848
N2AB	22696	68311;68312;68313	chr2:178573123;178573122;178573121	chr2:179437850;179437849;179437848
N2A	21769	65530;65531;65532	chr2:178573123;178573122;178573121	chr2:179437850;179437849;179437848
N2B	15272	46039;46040;46041	chr2:178573123;178573122;178573121	chr2:179437850;179437849;179437848
Novex-1	15397	46414;46415;46416	chr2:178573123;178573122;178573121	chr2:179437850;179437849;179437848
Novex-2	15464	46615;46616;46617	chr2:178573123;178573122;178573121	chr2:179437850;179437849;179437848
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-65
• Domain position: 15
• Structural Position: 17
• Q(SASA): 0.3828
• 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
R/T	None	None	0.684	N	0.485	0.129	0.263140351381	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

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
R/A	0.3186	likely_benign	0.2976	benign	-0.52	Destabilizing	0.373	N	0.462	neutral	None	None	None	None	N
R/C	0.1537	likely_benign	0.1508	benign	-0.483	Destabilizing	0.996	D	0.573	neutral	None	None	None	None	N
R/D	0.6949	likely_pathogenic	0.6441	pathogenic	-0.217	Destabilizing	0.742	D	0.499	neutral	None	None	None	None	N
R/E	0.4185	ambiguous	0.3782	ambiguous	-0.168	Destabilizing	0.373	N	0.459	neutral	None	None	None	None	N
R/F	0.6341	likely_pathogenic	0.5798	pathogenic	-0.822	Destabilizing	0.984	D	0.556	neutral	None	None	None	None	N
R/G	0.219	likely_benign	0.1985	benign	-0.713	Destabilizing	0.684	D	0.489	neutral	N	0.477805615	None	None	N
R/H	0.113	likely_benign	0.0998	benign	-1.09	Destabilizing	0.953	D	0.406	neutral	None	None	None	None	N
R/I	0.3541	ambiguous	0.3087	benign	-0.038	Destabilizing	0.939	D	0.563	neutral	N	0.475483388	None	None	N
R/K	0.0741	likely_benign	0.0747	benign	-0.516	Destabilizing	0.001	N	0.098	neutral	N	0.402462495	None	None	N
R/L	0.2932	likely_benign	0.2599	benign	-0.038	Destabilizing	0.742	D	0.489	neutral	None	None	None	None	N
R/M	0.3303	likely_benign	0.286	benign	-0.136	Destabilizing	0.984	D	0.455	neutral	None	None	None	None	N
R/N	0.5157	ambiguous	0.4496	ambiguous	-0.027	Destabilizing	0.742	D	0.447	neutral	None	None	None	None	N
R/P	0.4426	ambiguous	0.4158	ambiguous	-0.18	Destabilizing	0.953	D	0.51	neutral	None	None	None	None	N
R/Q	0.1111	likely_benign	0.1034	benign	-0.319	Destabilizing	0.742	D	0.503	neutral	None	None	None	None	N
R/S	0.3827	ambiguous	0.3414	ambiguous	-0.618	Destabilizing	0.684	D	0.481	neutral	N	0.413444705	None	None	N
R/T	0.2839	likely_benign	0.2342	benign	-0.438	Destabilizing	0.684	D	0.485	neutral	N	0.491561559	None	None	N
R/V	0.3992	ambiguous	0.3603	ambiguous	-0.18	Destabilizing	0.91	D	0.519	neutral	None	None	None	None	N
R/W	0.3449	ambiguous	0.2959	benign	-0.697	Destabilizing	0.996	D	0.667	neutral	None	None	None	None	N
R/Y	0.4659	ambiguous	0.4209	ambiguous	-0.318	Destabilizing	0.984	D	0.534	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.