TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14700	44323;44324;44325	chr2:178630860;178630859;178630858	chr2:179495587;179495586;179495585
N2AB	13059	39400;39401;39402	chr2:178630860;178630859;178630858	chr2:179495587;179495586;179495585
N2A	12132	36619;36620;36621	chr2:178630860;178630859;178630858	chr2:179495587;179495586;179495585
N2B	5635	17128;17129;17130	chr2:178630860;178630859;178630858	chr2:179495587;179495586;179495585
Novex-1	5760	17503;17504;17505	chr2:178630860;178630859;178630858	chr2:179495587;179495586;179495585
Novex-2	5827	17704;17705;17706	chr2:178630860;178630859;178630858	chr2:179495587;179495586;179495585
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAA
• RefSeq wild type template codon: CTT
• Domain: Ig-98
• Domain position: 26
• Structural Position: 41
• Q(SASA): 0.587
• 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
E/D	None	None	0.007	N	0.231	0.058	0.19670166235	gnomAD-4.0.0	1.59225E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	2.41779E-04	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
E/A	0.3379	likely_benign	0.3076	benign	-0.697	Destabilizing	0.7	D	0.663	prob.neutral	N	0.460008492	None	None	N
E/C	0.9367	likely_pathogenic	0.9367	pathogenic	-0.321	Destabilizing	0.996	D	0.829	deleterious	None	None	None	None	N
E/D	0.3855	ambiguous	0.4986	ambiguous	-0.864	Destabilizing	0.007	N	0.231	neutral	N	0.479247787	None	None	N
E/F	0.9152	likely_pathogenic	0.9286	pathogenic	-0.22	Destabilizing	0.996	D	0.791	deleterious	None	None	None	None	N
E/G	0.4155	ambiguous	0.4474	ambiguous	-1.022	Destabilizing	0.891	D	0.612	neutral	N	0.514892434	None	None	N
E/H	0.7007	likely_pathogenic	0.7198	pathogenic	-0.345	Destabilizing	0.996	D	0.727	deleterious	None	None	None	None	N
E/I	0.7242	likely_pathogenic	0.771	pathogenic	0.173	Stabilizing	0.956	D	0.806	deleterious	None	None	None	None	N
E/K	0.2783	likely_benign	0.2906	benign	-0.278	Destabilizing	0.7	D	0.595	neutral	N	0.504351693	None	None	N
E/L	0.7673	likely_pathogenic	0.8025	pathogenic	0.173	Stabilizing	0.956	D	0.726	deleterious	None	None	None	None	N
E/M	0.7556	likely_pathogenic	0.7659	pathogenic	0.468	Stabilizing	0.996	D	0.789	deleterious	None	None	None	None	N
E/N	0.66	likely_pathogenic	0.7002	pathogenic	-0.778	Destabilizing	0.844	D	0.756	deleterious	None	None	None	None	N
E/P	0.9682	likely_pathogenic	0.9837	pathogenic	-0.095	Destabilizing	0.956	D	0.756	deleterious	None	None	None	None	N
E/Q	0.281	likely_benign	0.2986	benign	-0.654	Destabilizing	0.891	D	0.722	deleterious	N	0.413856604	None	None	N
E/R	0.4453	ambiguous	0.469	ambiguous	-0.002	Destabilizing	0.956	D	0.735	deleterious	None	None	None	None	N
E/S	0.4853	ambiguous	0.496	ambiguous	-1.002	Destabilizing	0.607	D	0.621	neutral	None	None	None	None	N
E/T	0.5353	ambiguous	0.5597	ambiguous	-0.732	Destabilizing	0.916	D	0.72	deleterious	None	None	None	None	N
E/V	0.4703	ambiguous	0.5009	ambiguous	-0.095	Destabilizing	0.943	D	0.706	prob.delet.	N	0.507935314	None	None	N
E/W	0.9673	likely_pathogenic	0.9772	pathogenic	0.024	Stabilizing	0.996	D	0.812	deleterious	None	None	None	None	N
E/Y	0.8645	likely_pathogenic	0.893	pathogenic	0.033	Stabilizing	0.996	D	0.769	deleterious	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.