TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	13949	42070;42071;42072	chr2:178635479;178635478;178635477	chr2:179500206;179500205;179500204
N2AB	12308	37147;37148;37149	chr2:178635479;178635478;178635477	chr2:179500206;179500205;179500204
N2A	11381	34366;34367;34368	chr2:178635479;178635478;178635477	chr2:179500206;179500205;179500204
N2B	4884	14875;14876;14877	chr2:178635479;178635478;178635477	chr2:179500206;179500205;179500204
Novex-1	5009	15250;15251;15252	chr2:178635479;178635478;178635477	chr2:179500206;179500205;179500204
Novex-2	5076	15451;15452;15453	chr2:178635479;178635478;178635477	chr2:179500206;179500205;179500204
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-89
• Domain position: 74
• Structural Position: 158
• Q(SASA): 0.14
• 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
I/V	None	None	None	N	0.127	0.037	0.12205267543	gnomAD-4.0.0	6.87561E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	0	1.66317E-05

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	0.89	likely_pathogenic	0.8643	pathogenic	-2.676	Highly Destabilizing	0.134	N	0.509	neutral	None	None	None	None	N
I/C	0.9772	likely_pathogenic	0.9597	pathogenic	-1.994	Destabilizing	0.953	D	0.581	neutral	None	None	None	None	N
I/D	0.9983	likely_pathogenic	0.9982	pathogenic	-3.146	Highly Destabilizing	0.942	D	0.725	deleterious	None	None	None	None	N
I/E	0.9957	likely_pathogenic	0.9955	pathogenic	-2.927	Highly Destabilizing	0.842	D	0.727	deleterious	None	None	None	None	N
I/F	0.7793	likely_pathogenic	0.7139	pathogenic	-1.68	Destabilizing	0.664	D	0.597	neutral	N	0.454509128	None	None	N
I/G	0.9922	likely_pathogenic	0.9893	pathogenic	-3.222	Highly Destabilizing	0.603	D	0.69	prob.delet.	None	None	None	None	N
I/H	0.9972	likely_pathogenic	0.9961	pathogenic	-2.678	Highly Destabilizing	0.984	D	0.702	prob.delet.	None	None	None	None	N
I/K	0.9939	likely_pathogenic	0.993	pathogenic	-2.24	Highly Destabilizing	0.842	D	0.725	deleterious	None	None	None	None	N
I/L	0.4406	ambiguous	0.3841	ambiguous	-1.096	Destabilizing	0.022	N	0.369	neutral	N	0.447594833	None	None	N
I/M	0.3613	ambiguous	0.3438	ambiguous	-0.982	Destabilizing	0.664	D	0.625	neutral	N	0.455461947	None	None	N
I/N	0.9833	likely_pathogenic	0.9795	pathogenic	-2.571	Highly Destabilizing	0.924	D	0.746	deleterious	N	0.455681995	None	None	N
I/P	0.9976	likely_pathogenic	0.9973	pathogenic	-1.604	Destabilizing	0.942	D	0.722	deleterious	None	None	None	None	N
I/Q	0.995	likely_pathogenic	0.9935	pathogenic	-2.457	Highly Destabilizing	0.942	D	0.745	deleterious	None	None	None	None	N
I/R	0.9912	likely_pathogenic	0.9884	pathogenic	-1.864	Destabilizing	0.842	D	0.749	deleterious	None	None	None	None	N
I/S	0.9707	likely_pathogenic	0.9623	pathogenic	-3.241	Highly Destabilizing	0.361	N	0.618	neutral	N	0.454509128	None	None	N
I/T	0.8477	likely_pathogenic	0.8253	pathogenic	-2.876	Highly Destabilizing	0.361	N	0.542	neutral	N	0.44567276	None	None	N
I/V	0.1588	likely_benign	0.13	benign	-1.604	Destabilizing	None	N	0.127	neutral	N	0.358466792	None	None	N
I/W	0.9926	likely_pathogenic	0.9906	pathogenic	-2.105	Highly Destabilizing	0.984	D	0.726	deleterious	None	None	None	None	N
I/Y	0.977	likely_pathogenic	0.9659	pathogenic	-1.815	Destabilizing	0.842	D	0.631	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.