TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27021	81286;81287;81288	chr2:178565071;178565070;178565069	chr2:179429798;179429797;179429796
N2AB	25380	76363;76364;76365	chr2:178565071;178565070;178565069	chr2:179429798;179429797;179429796
N2A	24453	73582;73583;73584	chr2:178565071;178565070;178565069	chr2:179429798;179429797;179429796
N2B	17956	54091;54092;54093	chr2:178565071;178565070;178565069	chr2:179429798;179429797;179429796
Novex-1	18081	54466;54467;54468	chr2:178565071;178565070;178565069	chr2:179429798;179429797;179429796
Novex-2	18148	54667;54668;54669	chr2:178565071;178565070;178565069	chr2:179429798;179429797;179429796
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAC
• RefSeq wild type template codon: GTG
• Domain: Fn3-84
• Domain position: 50
• Structural Position: 66
• Q(SASA): 0.7787
• 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
H/Y	None	None	0.065	N	0.269	0.073	0.215869574891	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
H/A	0.1558	likely_benign	0.131	benign	-0.085	Destabilizing	0.004	N	0.264	neutral	None	None	None	None	N
H/C	0.1245	likely_benign	0.1126	benign	0.505	Stabilizing	0.788	D	0.261	neutral	None	None	None	None	N
H/D	0.1692	likely_benign	0.1483	benign	-0.315	Destabilizing	0.003	N	0.216	neutral	N	0.435844349	None	None	N
H/E	0.1658	likely_benign	0.1455	benign	-0.253	Destabilizing	None	N	0.085	neutral	None	None	None	None	N
H/F	0.2452	likely_benign	0.2073	benign	0.943	Stabilizing	0.22	N	0.323	neutral	None	None	None	None	N
H/G	0.2189	likely_benign	0.1938	benign	-0.41	Destabilizing	None	N	0.135	neutral	None	None	None	None	N
H/I	0.159	likely_benign	0.1353	benign	0.776	Stabilizing	0.085	N	0.387	neutral	None	None	None	None	N
H/K	0.1807	likely_benign	0.1751	benign	-0.075	Destabilizing	0.004	N	0.216	neutral	None	None	None	None	N
H/L	0.0808	likely_benign	0.0723	benign	0.776	Stabilizing	0.014	N	0.311	neutral	N	0.418354667	None	None	N
H/M	0.2223	likely_benign	0.1945	benign	0.508	Stabilizing	0.245	N	0.28	neutral	None	None	None	None	N
H/N	0.0607	likely_benign	0.0545	benign	-0.206	Destabilizing	None	N	0.103	neutral	N	0.43778579	None	None	N
H/P	0.6033	likely_pathogenic	0.58	pathogenic	0.513	Stabilizing	0.065	N	0.363	neutral	N	0.491948348	None	None	N
H/Q	0.0857	likely_benign	0.0787	benign	-0.034	Destabilizing	None	N	0.083	neutral	N	0.343606192	None	None	N
H/R	0.1179	likely_benign	0.1189	benign	-0.677	Destabilizing	0.007	N	0.206	neutral	N	0.400576983	None	None	N
H/S	0.1177	likely_benign	0.1031	benign	-0.088	Destabilizing	0.004	N	0.215	neutral	None	None	None	None	N
H/T	0.118	likely_benign	0.0977	benign	0.077	Stabilizing	0.009	N	0.281	neutral	None	None	None	None	N
H/V	0.118	likely_benign	0.1021	benign	0.513	Stabilizing	0.018	N	0.323	neutral	None	None	None	None	N
H/W	0.4329	ambiguous	0.4071	ambiguous	1.082	Stabilizing	0.788	D	0.255	neutral	None	None	None	None	N
H/Y	0.101	likely_benign	0.0877	benign	1.219	Stabilizing	0.065	N	0.269	neutral	N	0.438153936	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.