TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	28290	85093;85094;85095	chr2:178561264;178561263;178561262	chr2:179425991;179425990;179425989
N2AB	26649	80170;80171;80172	chr2:178561264;178561263;178561262	chr2:179425991;179425990;179425989
N2A	25722	77389;77390;77391	chr2:178561264;178561263;178561262	chr2:179425991;179425990;179425989
N2B	19225	57898;57899;57900	chr2:178561264;178561263;178561262	chr2:179425991;179425990;179425989
Novex-1	19350	58273;58274;58275	chr2:178561264;178561263;178561262	chr2:179425991;179425990;179425989
Novex-2	19417	58474;58475;58476	chr2:178561264;178561263;178561262	chr2:179425991;179425990;179425989
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: Fn3-94
• Domain position: 39
• Structural Position: 41
• Q(SASA): 0.0763
• 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/Q	None	None	1.0	N	0.756	0.395	0.276898752692	gnomAD-4.0.0	1.36846E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79891E-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
E/A	0.8641	likely_pathogenic	0.8713	pathogenic	-1.006	Destabilizing	0.999	D	0.693	prob.neutral	D	0.556587368	None	None	N
E/C	0.9855	likely_pathogenic	0.9866	pathogenic	-0.342	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/D	0.9067	likely_pathogenic	0.911	pathogenic	-1.741	Destabilizing	0.999	D	0.659	neutral	N	0.498907242	None	None	N
E/F	0.9895	likely_pathogenic	0.9891	pathogenic	-0.759	Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
E/G	0.9188	likely_pathogenic	0.9276	pathogenic	-1.387	Destabilizing	1.0	D	0.747	deleterious	D	0.54025754	None	None	N
E/H	0.9766	likely_pathogenic	0.9766	pathogenic	-0.68	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	N
E/I	0.973	likely_pathogenic	0.9729	pathogenic	0.082	Stabilizing	1.0	D	0.823	deleterious	None	None	None	None	N
E/K	0.9469	likely_pathogenic	0.9502	pathogenic	-1.135	Destabilizing	0.999	D	0.679	prob.neutral	N	0.509730115	None	None	N
E/L	0.9643	likely_pathogenic	0.9705	pathogenic	0.082	Stabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
E/M	0.9507	likely_pathogenic	0.9544	pathogenic	0.695	Stabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
E/N	0.9801	likely_pathogenic	0.9805	pathogenic	-1.442	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/P	0.9995	likely_pathogenic	0.9996	pathogenic	-0.266	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
E/Q	0.6491	likely_pathogenic	0.6415	pathogenic	-1.108	Destabilizing	1.0	D	0.756	deleterious	N	0.482889674	None	None	N
E/R	0.9638	likely_pathogenic	0.9668	pathogenic	-1.099	Destabilizing	1.0	D	0.791	deleterious	None	None	None	None	N
E/S	0.8906	likely_pathogenic	0.8907	pathogenic	-1.955	Destabilizing	0.999	D	0.73	prob.delet.	None	None	None	None	N
E/T	0.9586	likely_pathogenic	0.9603	pathogenic	-1.588	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	N
E/V	0.9357	likely_pathogenic	0.9365	pathogenic	-0.266	Destabilizing	1.0	D	0.751	deleterious	D	0.525418514	None	None	N
E/W	0.9964	likely_pathogenic	0.9966	pathogenic	-0.979	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
E/Y	0.9842	likely_pathogenic	0.9835	pathogenic	-0.607	Destabilizing	1.0	D	0.795	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.