TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21402	64429;64430;64431	chr2:178586697;178586696;178586695	chr2:179451424;179451423;179451422
N2AB	19761	59506;59507;59508	chr2:178586697;178586696;178586695	chr2:179451424;179451423;179451422
N2A	18834	56725;56726;56727	chr2:178586697;178586696;178586695	chr2:179451424;179451423;179451422
N2B	12337	37234;37235;37236	chr2:178586697;178586696;178586695	chr2:179451424;179451423;179451422
Novex-1	12462	37609;37610;37611	chr2:178586697;178586696;178586695	chr2:179451424;179451423;179451422
Novex-2	12529	37810;37811;37812	chr2:178586697;178586696;178586695	chr2:179451424;179451423;179451422
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-43
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.2784
• 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
I/V	rs1157697777	-1.231	0.002	N	0.248	0.086	0.42264334713	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
I/V	rs1157697777	-1.231	0.002	N	0.248	0.086	0.42264334713	gnomAD-4.0.0	4.77809E-06	None	None	None	None	I	None	0	4.5754E-05	None	0	0	None	1.88253E-05	0	0	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
I/A	0.8365	likely_pathogenic	0.7824	pathogenic	-2.075	Highly Destabilizing	0.525	D	0.487	neutral	None	None	None	None	I
I/C	0.8509	likely_pathogenic	0.8253	pathogenic	-1.55	Destabilizing	0.998	D	0.578	neutral	None	None	None	None	I
I/D	0.9681	likely_pathogenic	0.9518	pathogenic	-1.785	Destabilizing	0.991	D	0.638	neutral	None	None	None	None	I
I/E	0.8708	likely_pathogenic	0.8162	pathogenic	-1.731	Destabilizing	0.974	D	0.635	neutral	None	None	None	None	I
I/F	0.3557	ambiguous	0.3063	benign	-1.406	Destabilizing	0.934	D	0.527	neutral	N	0.49877832	None	None	I
I/G	0.9622	likely_pathogenic	0.9492	pathogenic	-2.443	Highly Destabilizing	0.974	D	0.634	neutral	None	None	None	None	I
I/H	0.7886	likely_pathogenic	0.7338	pathogenic	-1.534	Destabilizing	0.998	D	0.657	neutral	None	None	None	None	I
I/K	0.7052	likely_pathogenic	0.6246	pathogenic	-1.429	Destabilizing	0.974	D	0.637	neutral	None	None	None	None	I
I/L	0.2002	likely_benign	0.1873	benign	-1.098	Destabilizing	0.005	N	0.271	neutral	N	0.480403203	None	None	I
I/M	0.2321	likely_benign	0.2057	benign	-1.012	Destabilizing	0.934	D	0.543	neutral	N	0.479597991	None	None	I
I/N	0.759	likely_pathogenic	0.6985	pathogenic	-1.397	Destabilizing	0.989	D	0.649	neutral	N	0.464390118	None	None	I
I/P	0.9936	likely_pathogenic	0.9921	pathogenic	-1.396	Destabilizing	0.991	D	0.635	neutral	None	None	None	None	I
I/Q	0.7509	likely_pathogenic	0.6781	pathogenic	-1.561	Destabilizing	0.991	D	0.641	neutral	None	None	None	None	I
I/R	0.6304	likely_pathogenic	0.5476	ambiguous	-0.827	Destabilizing	0.991	D	0.649	neutral	None	None	None	None	I
I/S	0.7663	likely_pathogenic	0.7067	pathogenic	-2.081	Highly Destabilizing	0.966	D	0.611	neutral	N	0.518516087	None	None	I
I/T	0.6335	likely_pathogenic	0.562	ambiguous	-1.908	Destabilizing	0.801	D	0.521	neutral	N	0.491638917	None	None	I
I/V	0.0986	likely_benign	0.0929	benign	-1.396	Destabilizing	0.002	N	0.248	neutral	N	0.421760331	None	None	I
I/W	0.9076	likely_pathogenic	0.8974	pathogenic	-1.481	Destabilizing	0.998	D	0.688	prob.neutral	None	None	None	None	I
I/Y	0.7402	likely_pathogenic	0.6826	pathogenic	-1.259	Destabilizing	0.991	D	0.588	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.