TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18571	55936;55937;55938	chr2:178601286;178601285;178601284	chr2:179466013;179466012;179466011
N2AB	16930	51013;51014;51015	chr2:178601286;178601285;178601284	chr2:179466013;179466012;179466011
N2A	16003	48232;48233;48234	chr2:178601286;178601285;178601284	chr2:179466013;179466012;179466011
N2B	9506	28741;28742;28743	chr2:178601286;178601285;178601284	chr2:179466013;179466012;179466011
Novex-1	9631	29116;29117;29118	chr2:178601286;178601285;178601284	chr2:179466013;179466012;179466011
Novex-2	9698	29317;29318;29319	chr2:178601286;178601285;178601284	chr2:179466013;179466012;179466011
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-22
• Domain position: 93
• Structural Position: 127
• Q(SASA): 0.2516
• 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
T/I	None	None	0.728	N	0.552	0.177	0.32053947749	gnomAD-4.0.0	2.1328E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.75815E-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
T/A	0.1535	likely_benign	0.1594	benign	-0.889	Destabilizing	0.029	N	0.209	neutral	N	0.484982304	None	None	N
T/C	0.4512	ambiguous	0.5152	ambiguous	-0.569	Destabilizing	0.998	D	0.598	neutral	None	None	None	None	N
T/D	0.9081	likely_pathogenic	0.9061	pathogenic	-0.811	Destabilizing	0.981	D	0.592	neutral	None	None	None	None	N
T/E	0.7684	likely_pathogenic	0.78	pathogenic	-0.622	Destabilizing	0.935	D	0.542	neutral	None	None	None	None	N
T/F	0.5463	ambiguous	0.5471	ambiguous	-0.603	Destabilizing	0.981	D	0.645	neutral	None	None	None	None	N
T/G	0.617	likely_pathogenic	0.6381	pathogenic	-1.3	Destabilizing	0.876	D	0.568	neutral	None	None	None	None	N
T/H	0.6508	likely_pathogenic	0.6543	pathogenic	-1.261	Destabilizing	0.998	D	0.653	prob.neutral	None	None	None	None	N
T/I	0.2307	likely_benign	0.2278	benign	0.182	Stabilizing	0.728	D	0.552	neutral	N	0.41800795	None	None	N
T/K	0.7212	likely_pathogenic	0.7075	pathogenic	-0.352	Destabilizing	0.935	D	0.555	neutral	None	None	None	None	N
T/L	0.2329	likely_benign	0.2081	benign	0.182	Stabilizing	0.594	D	0.506	neutral	None	None	None	None	N
T/M	0.1524	likely_benign	0.1416	benign	0.099	Stabilizing	0.981	D	0.595	neutral	None	None	None	None	N
T/N	0.5063	ambiguous	0.5111	ambiguous	-1.001	Destabilizing	0.991	D	0.57	neutral	N	0.485849095	None	None	N
T/P	0.7864	likely_pathogenic	0.6843	pathogenic	-0.143	Destabilizing	0.974	D	0.592	neutral	N	0.485849095	None	None	N
T/Q	0.5843	likely_pathogenic	0.6025	pathogenic	-0.767	Destabilizing	0.994	D	0.599	neutral	None	None	None	None	N
T/R	0.705	likely_pathogenic	0.6785	pathogenic	-0.51	Destabilizing	0.981	D	0.574	neutral	None	None	None	None	N
T/S	0.3033	likely_benign	0.3261	benign	-1.31	Destabilizing	0.728	D	0.552	neutral	N	0.484808945	None	None	N
T/V	0.1434	likely_benign	0.1523	benign	-0.143	Destabilizing	0.038	N	0.179	neutral	None	None	None	None	N
T/W	0.8804	likely_pathogenic	0.8675	pathogenic	-0.727	Destabilizing	0.998	D	0.691	prob.delet.	None	None	None	None	N
T/Y	0.6065	likely_pathogenic	0.634	pathogenic	-0.338	Destabilizing	0.994	D	0.665	prob.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.