TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19883	59872;59873;59874	chr2:178592257;178592256;178592255	chr2:179456984;179456983;179456982
N2AB	18242	54949;54950;54951	chr2:178592257;178592256;178592255	chr2:179456984;179456983;179456982
N2A	17315	52168;52169;52170	chr2:178592257;178592256;178592255	chr2:179456984;179456983;179456982
N2B	10818	32677;32678;32679	chr2:178592257;178592256;178592255	chr2:179456984;179456983;179456982
Novex-1	10943	33052;33053;33054	chr2:178592257;178592256;178592255	chr2:179456984;179456983;179456982
Novex-2	11010	33253;33254;33255	chr2:178592257;178592256;178592255	chr2:179456984;179456983;179456982
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-32
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.5735
• 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
D/Y	rs1060500395	None	0.934	N	0.461	0.377	None	gnomAD-4.0.0	1.0963E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.35016E-05	0	1.6592E-05

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
D/A	0.171	likely_benign	0.1666	benign	-0.395	Destabilizing	0.801	D	0.364	neutral	N	0.473786662	None	None	N
D/C	0.5147	ambiguous	0.5192	ambiguous	-0.149	Destabilizing	0.998	D	0.524	neutral	None	None	None	None	N
D/E	0.1709	likely_benign	0.1583	benign	-0.472	Destabilizing	0.625	D	0.368	neutral	N	0.498394318	None	None	N
D/F	0.4626	ambiguous	0.4465	ambiguous	-0.224	Destabilizing	0.974	D	0.458	neutral	None	None	None	None	N
D/G	0.1405	likely_benign	0.1497	benign	-0.63	Destabilizing	0.669	D	0.334	neutral	N	0.479576484	None	None	N
D/H	0.2255	likely_benign	0.2412	benign	-0.179	Destabilizing	0.012	N	0.193	neutral	N	0.464052458	None	None	N
D/I	0.4259	ambiguous	0.4227	ambiguous	0.188	Stabilizing	0.974	D	0.465	neutral	None	None	None	None	N
D/K	0.4203	ambiguous	0.432	ambiguous	0.015	Stabilizing	0.842	D	0.367	neutral	None	None	None	None	N
D/L	0.3464	ambiguous	0.3355	benign	0.188	Stabilizing	0.974	D	0.408	neutral	None	None	None	None	N
D/M	0.5472	ambiguous	0.535	ambiguous	0.334	Stabilizing	0.998	D	0.454	neutral	None	None	None	None	N
D/N	0.0763	likely_benign	0.0795	benign	-0.298	Destabilizing	0.005	N	0.073	neutral	N	0.409596324	None	None	N
D/P	0.8223	likely_pathogenic	0.8611	pathogenic	0.017	Stabilizing	0.991	D	0.449	neutral	None	None	None	None	N
D/Q	0.2827	likely_benign	0.2894	benign	-0.259	Destabilizing	0.974	D	0.4	neutral	None	None	None	None	N
D/R	0.4343	ambiguous	0.451	ambiguous	0.238	Stabilizing	0.949	D	0.398	neutral	None	None	None	None	N
D/S	0.1314	likely_benign	0.135	benign	-0.436	Destabilizing	0.728	D	0.32	neutral	None	None	None	None	N
D/T	0.2972	likely_benign	0.3051	benign	-0.258	Destabilizing	0.842	D	0.365	neutral	None	None	None	None	N
D/V	0.2801	likely_benign	0.2739	benign	0.017	Stabilizing	0.966	D	0.441	neutral	N	0.501666697	None	None	N
D/W	0.84	likely_pathogenic	0.8403	pathogenic	-0.065	Destabilizing	0.998	D	0.62	neutral	None	None	None	None	N
D/Y	0.1871	likely_benign	0.1831	benign	0.009	Stabilizing	0.934	D	0.461	neutral	N	0.495046128	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.