TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24203	72832;72833;72834	chr2:178573525;178573524;178573523	chr2:179438252;179438251;179438250
N2AB	22562	67909;67910;67911	chr2:178573525;178573524;178573523	chr2:179438252;179438251;179438250
N2A	21635	65128;65129;65130	chr2:178573525;178573524;178573523	chr2:179438252;179438251;179438250
N2B	15138	45637;45638;45639	chr2:178573525;178573524;178573523	chr2:179438252;179438251;179438250
Novex-1	15263	46012;46013;46014	chr2:178573525;178573524;178573523	chr2:179438252;179438251;179438250
Novex-2	15330	46213;46214;46215	chr2:178573525;178573524;178573523	chr2:179438252;179438251;179438250
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-63
• Domain position: 82
• Structural Position: 114
• Q(SASA): 0.6212
• Predicted PPI site: I

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
Y/F	rs1235190476	-0.166	0.892	N	0.535	0.267	0.427024044652	gnomAD-2.1.1	6.38E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.29719E-04	0
Y/F	rs1235190476	-0.166	0.892	N	0.535	0.267	0.427024044652	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	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
Y/A	0.9036	likely_pathogenic	0.9138	pathogenic	-0.619	Destabilizing	0.916	D	0.656	neutral	None	None	None	None	I
Y/C	0.4622	ambiguous	0.5381	ambiguous	0.135	Stabilizing	0.999	D	0.697	prob.neutral	D	0.524002052	None	None	I
Y/D	0.8816	likely_pathogenic	0.8918	pathogenic	0.868	Stabilizing	0.994	D	0.687	prob.neutral	N	0.485279076	None	None	I
Y/E	0.9622	likely_pathogenic	0.9675	pathogenic	0.85	Stabilizing	0.987	D	0.672	neutral	None	None	None	None	I
Y/F	0.0978	likely_benign	0.0922	benign	-0.311	Destabilizing	0.892	D	0.535	neutral	N	0.47776833	None	None	I
Y/G	0.9161	likely_pathogenic	0.9279	pathogenic	-0.806	Destabilizing	0.987	D	0.667	neutral	None	None	None	None	I
Y/H	0.5328	ambiguous	0.5612	ambiguous	0.22	Stabilizing	0.994	D	0.596	neutral	N	0.470252694	None	None	I
Y/I	0.6985	likely_pathogenic	0.729	pathogenic	-0.15	Destabilizing	0.95	D	0.637	neutral	None	None	None	None	I
Y/K	0.9682	likely_pathogenic	0.9735	pathogenic	0.224	Stabilizing	0.975	D	0.665	neutral	None	None	None	None	I
Y/L	0.7836	likely_pathogenic	0.8026	pathogenic	-0.15	Destabilizing	0.437	N	0.6	neutral	None	None	None	None	I
Y/M	0.8047	likely_pathogenic	0.8181	pathogenic	-0.056	Destabilizing	0.693	D	0.57	neutral	None	None	None	None	I
Y/N	0.5892	likely_pathogenic	0.614	pathogenic	0.034	Stabilizing	0.983	D	0.678	prob.neutral	N	0.471542914	None	None	I
Y/P	0.992	likely_pathogenic	0.9938	pathogenic	-0.287	Destabilizing	0.996	D	0.702	prob.neutral	None	None	None	None	I
Y/Q	0.9261	likely_pathogenic	0.9401	pathogenic	0.085	Stabilizing	0.987	D	0.639	neutral	None	None	None	None	I
Y/R	0.9288	likely_pathogenic	0.9411	pathogenic	0.45	Stabilizing	0.987	D	0.679	prob.neutral	None	None	None	None	I
Y/S	0.7959	likely_pathogenic	0.811	pathogenic	-0.379	Destabilizing	0.967	D	0.621	neutral	N	0.518921519	None	None	I
Y/T	0.9031	likely_pathogenic	0.9187	pathogenic	-0.304	Destabilizing	0.975	D	0.65	neutral	None	None	None	None	I
Y/V	0.6569	likely_pathogenic	0.6922	pathogenic	-0.287	Destabilizing	0.845	D	0.643	neutral	None	None	None	None	I
Y/W	0.5923	likely_pathogenic	0.5728	pathogenic	-0.451	Destabilizing	0.999	D	0.584	neutral	None	None	None	None	I

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.