TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19024	57295;57296;57297	chr2:178598547;178598546;178598545	chr2:179463274;179463273;179463272
N2AB	17383	52372;52373;52374	chr2:178598547;178598546;178598545	chr2:179463274;179463273;179463272
N2A	16456	49591;49592;49593	chr2:178598547;178598546;178598545	chr2:179463274;179463273;179463272
N2B	9959	30100;30101;30102	chr2:178598547;178598546;178598545	chr2:179463274;179463273;179463272
Novex-1	10084	30475;30476;30477	chr2:178598547;178598546;178598545	chr2:179463274;179463273;179463272
Novex-2	10151	30676;30677;30678	chr2:178598547;178598546;178598545	chr2:179463274;179463273;179463272
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: Fn3-26
• Domain position: 37
• Structural Position: 39
• Q(SASA): 0.2049
• 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	rs876658068	None	0.022	N	0.324	0.087	0.430126000877	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	2.41E-05	1.31062E-04	0	0	0	None	0	0	1.47E-05	0	0
I/V	rs876658068	None	0.022	N	0.324	0.087	0.430126000877	gnomAD-4.0.0	6.09015E-06	None	None	None	None	N	None	1.74758E-05	1.23122E-04	None	0	0	None	0	0	1.20497E-06	9.39496E-05	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	0.3419	ambiguous	0.3448	ambiguous	-2.66	Highly Destabilizing	0.688	D	0.633	neutral	None	None	None	None	N
I/C	0.6047	likely_pathogenic	0.6232	pathogenic	-1.948	Destabilizing	0.998	D	0.679	prob.neutral	None	None	None	None	N
I/D	0.7844	likely_pathogenic	0.785	pathogenic	-2.962	Highly Destabilizing	0.991	D	0.7	prob.neutral	None	None	None	None	N
I/E	0.6043	likely_pathogenic	0.5781	pathogenic	-2.798	Highly Destabilizing	0.991	D	0.689	prob.neutral	None	None	None	None	N
I/F	0.1007	likely_benign	0.1073	benign	-1.564	Destabilizing	0.005	N	0.404	neutral	N	0.461876158	None	None	N
I/G	0.7957	likely_pathogenic	0.7895	pathogenic	-3.145	Highly Destabilizing	0.974	D	0.682	prob.neutral	None	None	None	None	N
I/H	0.4219	ambiguous	0.4351	ambiguous	-2.454	Highly Destabilizing	0.998	D	0.709	prob.delet.	None	None	None	None	N
I/K	0.5044	ambiguous	0.4792	ambiguous	-2.159	Highly Destabilizing	0.991	D	0.691	prob.neutral	None	None	None	None	N
I/L	0.1141	likely_benign	0.1027	benign	-1.278	Destabilizing	0.267	N	0.531	neutral	N	0.472322438	None	None	N
I/M	0.0979	likely_benign	0.097	benign	-1.205	Destabilizing	0.986	D	0.711	prob.delet.	N	0.467747934	None	None	N
I/N	0.4107	ambiguous	0.4171	ambiguous	-2.324	Highly Destabilizing	0.989	D	0.712	prob.delet.	N	0.499719683	None	None	N
I/P	0.9821	likely_pathogenic	0.9837	pathogenic	-1.718	Destabilizing	0.991	D	0.713	prob.delet.	None	None	None	None	N
I/Q	0.4947	ambiguous	0.4753	ambiguous	-2.304	Highly Destabilizing	0.991	D	0.707	prob.neutral	None	None	None	None	N
I/R	0.364	ambiguous	0.3456	ambiguous	-1.666	Destabilizing	0.991	D	0.711	prob.delet.	None	None	None	None	N
I/S	0.3387	likely_benign	0.3378	benign	-2.98	Highly Destabilizing	0.891	D	0.664	neutral	N	0.499660968	None	None	N
I/T	0.1462	likely_benign	0.1465	benign	-2.691	Highly Destabilizing	0.801	D	0.654	neutral	N	0.480864563	None	None	N
I/V	0.0699	likely_benign	0.0718	benign	-1.718	Destabilizing	0.022	N	0.324	neutral	N	0.421490972	None	None	N
I/W	0.5597	ambiguous	0.5793	pathogenic	-1.891	Destabilizing	0.998	D	0.702	prob.neutral	None	None	None	None	N
I/Y	0.3596	ambiguous	0.3577	ambiguous	-1.678	Destabilizing	0.728	D	0.677	prob.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.