TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23501	70726;70727;70728	chr2:178575631;178575630;178575629	chr2:179440358;179440357;179440356
N2AB	21860	65803;65804;65805	chr2:178575631;178575630;178575629	chr2:179440358;179440357;179440356
N2A	20933	63022;63023;63024	chr2:178575631;178575630;178575629	chr2:179440358;179440357;179440356
N2B	14436	43531;43532;43533	chr2:178575631;178575630;178575629	chr2:179440358;179440357;179440356
Novex-1	14561	43906;43907;43908	chr2:178575631;178575630;178575629	chr2:179440358;179440357;179440356
Novex-2	14628	44107;44108;44109	chr2:178575631;178575630;178575629	chr2:179440358;179440357;179440356
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: Fn3-58
• Domain position: 67
• Structural Position: 99
• Q(SASA): 0.5615
• 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	rs1709809170	None	0.997	N	0.71	0.361	0.48087575253	gnomAD-4.0.0	4.77544E-06	None	None	None	None	N	None	0	2.28655E-05	None	0	0	None	0	0	0	2.86615E-05	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	0.2605	likely_benign	0.291	benign	-0.204	Destabilizing	0.995	D	0.647	neutral	N	0.517209365	None	None	N
E/C	0.9534	likely_pathogenic	0.9653	pathogenic	0.247	Stabilizing	1.0	D	0.655	neutral	None	None	None	None	N
E/D	0.5737	likely_pathogenic	0.5325	ambiguous	-0.208	Destabilizing	0.965	D	0.603	neutral	N	0.504414197	None	None	N
E/F	0.9697	likely_pathogenic	0.9763	pathogenic	-0.31	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
E/G	0.5086	ambiguous	0.5549	ambiguous	-0.363	Destabilizing	1.0	D	0.6	neutral	N	0.510263547	None	None	N
E/H	0.8794	likely_pathogenic	0.9021	pathogenic	-0.133	Destabilizing	1.0	D	0.626	neutral	None	None	None	None	N
E/I	0.6899	likely_pathogenic	0.7366	pathogenic	0.166	Stabilizing	0.999	D	0.627	neutral	None	None	None	None	N
E/K	0.4001	ambiguous	0.4763	ambiguous	0.569	Stabilizing	0.997	D	0.71	prob.delet.	N	0.474598015	None	None	N
E/L	0.803	likely_pathogenic	0.849	pathogenic	0.166	Stabilizing	0.999	D	0.621	neutral	None	None	None	None	N
E/M	0.7806	likely_pathogenic	0.8179	pathogenic	0.322	Stabilizing	0.998	D	0.585	neutral	None	None	None	None	N
E/N	0.7557	likely_pathogenic	0.7622	pathogenic	0.388	Stabilizing	0.998	D	0.682	prob.neutral	None	None	None	None	N
E/P	0.5936	likely_pathogenic	0.642	pathogenic	0.063	Stabilizing	0.992	D	0.604	neutral	None	None	None	None	N
E/Q	0.2979	likely_benign	0.3224	benign	0.39	Stabilizing	0.999	D	0.685	prob.neutral	N	0.48340988	None	None	N
E/R	0.5834	likely_pathogenic	0.6683	pathogenic	0.623	Stabilizing	0.999	D	0.675	neutral	None	None	None	None	N
E/S	0.4747	ambiguous	0.4987	ambiguous	0.228	Stabilizing	0.997	D	0.698	prob.neutral	None	None	None	None	N
E/T	0.5356	ambiguous	0.58	pathogenic	0.357	Stabilizing	0.999	D	0.636	neutral	None	None	None	None	N
E/V	0.4556	ambiguous	0.5035	ambiguous	0.063	Stabilizing	0.998	D	0.603	neutral	N	0.493057892	None	None	N
E/W	0.9924	likely_pathogenic	0.9945	pathogenic	-0.243	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	N
E/Y	0.9567	likely_pathogenic	0.9651	pathogenic	-0.074	Destabilizing	1.0	D	0.592	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.