TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16617	50074;50075;50076	chr2:178612872;178612871;178612870	chr2:179477599;179477598;179477597
N2AB	14976	45151;45152;45153	chr2:178612872;178612871;178612870	chr2:179477599;179477598;179477597
N2A	14049	42370;42371;42372	chr2:178612872;178612871;178612870	chr2:179477599;179477598;179477597
N2B	7552	22879;22880;22881	chr2:178612872;178612871;178612870	chr2:179477599;179477598;179477597
Novex-1	7677	23254;23255;23256	chr2:178612872;178612871;178612870	chr2:179477599;179477598;179477597
Novex-2	7744	23455;23456;23457	chr2:178612872;178612871;178612870	chr2:179477599;179477598;179477597
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: Fn3-8
• Domain position: 67
• Structural Position: 99
• Q(SASA): 0.4683
• 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/K	None	None	0.998	D	0.556	0.308	0.383921772103	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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	0.2304	likely_benign	0.2585	benign	-0.456	Destabilizing	0.996	D	0.502	neutral	N	0.501076795	None	None	N
E/C	0.9642	likely_pathogenic	0.9695	pathogenic	0.032	Stabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/D	0.321	likely_benign	0.2901	benign	-0.422	Destabilizing	0.998	D	0.502	neutral	D	0.53767553	None	None	N
E/F	0.9556	likely_pathogenic	0.9589	pathogenic	-0.396	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
E/G	0.4278	ambiguous	0.4766	ambiguous	-0.676	Destabilizing	0.999	D	0.525	neutral	D	0.611875146	None	None	N
E/H	0.8586	likely_pathogenic	0.8794	pathogenic	-0.373	Destabilizing	1.0	D	0.575	neutral	None	None	None	None	N
E/I	0.6975	likely_pathogenic	0.7016	pathogenic	0.098	Stabilizing	1.0	D	0.665	neutral	None	None	None	None	N
E/K	0.5053	ambiguous	0.5663	pathogenic	0.22	Stabilizing	0.998	D	0.556	neutral	D	0.535494756	None	None	N
E/L	0.7644	likely_pathogenic	0.772	pathogenic	0.098	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	N
E/M	0.7854	likely_pathogenic	0.7974	pathogenic	0.341	Stabilizing	1.0	D	0.591	neutral	None	None	None	None	N
E/N	0.604	likely_pathogenic	0.6097	pathogenic	-0.034	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
E/P	0.5425	ambiguous	0.5852	pathogenic	-0.066	Destabilizing	0.504	D	0.294	neutral	None	None	None	None	N
E/Q	0.3254	likely_benign	0.3605	ambiguous	-0.006	Destabilizing	1.0	D	0.617	neutral	N	0.474985199	None	None	N
E/R	0.6577	likely_pathogenic	0.73	pathogenic	0.358	Stabilizing	1.0	D	0.602	neutral	None	None	None	None	N
E/S	0.4262	ambiguous	0.455	ambiguous	-0.231	Destabilizing	0.998	D	0.571	neutral	None	None	None	None	N
E/T	0.4936	ambiguous	0.5291	ambiguous	-0.055	Destabilizing	1.0	D	0.537	neutral	None	None	None	None	N
E/V	0.4369	ambiguous	0.4582	ambiguous	-0.066	Destabilizing	0.999	D	0.56	neutral	D	0.546921974	None	None	N
E/W	0.9866	likely_pathogenic	0.9897	pathogenic	-0.259	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	N
E/Y	0.9209	likely_pathogenic	0.9312	pathogenic	-0.155	Destabilizing	1.0	D	0.6	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.