TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19292	58099;58100;58101	chr2:178594620;178594619;178594618	chr2:179459347;179459346;179459345
N2AB	17651	53176;53177;53178	chr2:178594620;178594619;178594618	chr2:179459347;179459346;179459345
N2A	16724	50395;50396;50397	chr2:178594620;178594619;178594618	chr2:179459347;179459346;179459345
N2B	10227	30904;30905;30906	chr2:178594620;178594619;178594618	chr2:179459347;179459346;179459345
Novex-1	10352	31279;31280;31281	chr2:178594620;178594619;178594618	chr2:179459347;179459346;179459345
Novex-2	10419	31480;31481;31482	chr2:178594620;178594619;178594618	chr2:179459347;179459346;179459345
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: Fn3-28
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.4915
• 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/A	rs1225953212	-0.555	0.625	N	0.476	0.141	0.300110245524	gnomAD-2.1.1	4.05E-06	None	None	None	None	N	None	0	2.92E-05	None	0	0	None	0	None	0	0	0
E/A	rs1225953212	-0.555	0.625	N	0.476	0.141	0.300110245524	gnomAD-4.0.0	1.59757E-06	None	None	None	None	N	None	0	2.29632E-05	None	0	0	None	0	0	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	0.1329	likely_benign	0.1515	benign	-0.717	Destabilizing	0.625	D	0.476	neutral	N	0.509360673	None	None	N
E/C	0.7523	likely_pathogenic	0.7869	pathogenic	-0.264	Destabilizing	0.998	D	0.613	neutral	None	None	None	None	N
E/D	0.208	likely_benign	0.202	benign	-0.76	Destabilizing	0.801	D	0.561	neutral	N	0.469229191	None	None	N
E/F	0.6692	likely_pathogenic	0.7021	pathogenic	-0.378	Destabilizing	0.974	D	0.636	neutral	None	None	None	None	N
E/G	0.2795	likely_benign	0.2914	benign	-1.008	Destabilizing	0.801	D	0.602	neutral	N	0.479775802	None	None	N
E/H	0.4081	ambiguous	0.4314	ambiguous	-0.466	Destabilizing	0.974	D	0.629	neutral	None	None	None	None	N
E/I	0.1975	likely_benign	0.2268	benign	0.05	Stabilizing	0.029	N	0.413	neutral	None	None	None	None	N
E/K	0.177	likely_benign	0.1877	benign	-0.21	Destabilizing	0.669	D	0.579	neutral	N	0.445423838	None	None	N
E/L	0.2711	likely_benign	0.3097	benign	0.05	Stabilizing	0.525	D	0.449	neutral	None	None	None	None	N
E/M	0.3189	likely_benign	0.3665	ambiguous	0.367	Stabilizing	0.974	D	0.617	neutral	None	None	None	None	N
E/N	0.2771	likely_benign	0.3137	benign	-0.61	Destabilizing	0.949	D	0.637	neutral	None	None	None	None	N
E/P	0.9622	likely_pathogenic	0.9693	pathogenic	-0.184	Destabilizing	0.974	D	0.655	neutral	None	None	None	None	N
E/Q	0.1099	likely_benign	0.1271	benign	-0.53	Destabilizing	0.051	N	0.286	neutral	N	0.500335758	None	None	N
E/R	0.2903	likely_benign	0.2927	benign	0.043	Stabilizing	0.904	D	0.634	neutral	None	None	None	None	N
E/S	0.2075	likely_benign	0.2356	benign	-0.837	Destabilizing	0.842	D	0.588	neutral	None	None	None	None	N
E/T	0.1537	likely_benign	0.179	benign	-0.601	Destabilizing	0.842	D	0.59	neutral	None	None	None	None	N
E/V	0.1244	likely_benign	0.1393	benign	-0.184	Destabilizing	0.051	N	0.339	neutral	N	0.49167899	None	None	N
E/W	0.8907	likely_pathogenic	0.8956	pathogenic	-0.152	Destabilizing	0.998	D	0.649	neutral	None	None	None	None	N
E/Y	0.605	likely_pathogenic	0.6206	pathogenic	-0.13	Destabilizing	0.991	D	0.637	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.