TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16962	51109;51110;51111	chr2:178611245;178611244;178611243	chr2:179475972;179475971;179475970
N2AB	15321	46186;46187;46188	chr2:178611245;178611244;178611243	chr2:179475972;179475971;179475970
N2A	14394	43405;43406;43407	chr2:178611245;178611244;178611243	chr2:179475972;179475971;179475970
N2B	7897	23914;23915;23916	chr2:178611245;178611244;178611243	chr2:179475972;179475971;179475970
Novex-1	8022	24289;24290;24291	chr2:178611245;178611244;178611243	chr2:179475972;179475971;179475970
Novex-2	8089	24490;24491;24492	chr2:178611245;178611244;178611243	chr2:179475972;179475971;179475970
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Ig-111
• Domain position: 8
• Structural Position: 9
• Q(SASA): 0.5653
• 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/R	None	None	0.002	N	0.126	0.174	0.277730125212	gnomAD-4.0.0	2.05429E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69965E-06	0	0
H/Y	None	None	0.917	N	0.283	0.204	0.365317461125	gnomAD-4.0.0	3.18884E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88587E-05	0	2.86256E-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	0.1564	likely_benign	0.1524	benign	0.389	Stabilizing	0.176	N	0.245	neutral	None	None	None	None	N
H/C	0.1587	likely_benign	0.163	benign	0.739	Stabilizing	0.995	D	0.299	neutral	None	None	None	None	N
H/D	0.1266	likely_benign	0.124	benign	0.168	Stabilizing	0.642	D	0.341	neutral	N	0.423746512	None	None	N
H/E	0.1555	likely_benign	0.1527	benign	0.193	Stabilizing	0.329	N	0.193	neutral	None	None	None	None	N
H/F	0.3652	ambiguous	0.3683	ambiguous	1.034	Stabilizing	0.704	D	0.392	neutral	None	None	None	None	N
H/G	0.1749	likely_benign	0.1725	benign	0.113	Stabilizing	0.495	N	0.29	neutral	None	None	None	None	N
H/I	0.3035	likely_benign	0.31	benign	1.088	Stabilizing	0.543	D	0.39	neutral	None	None	None	None	N
H/K	0.1129	likely_benign	0.1201	benign	0.399	Stabilizing	0.013	N	0.12	neutral	None	None	None	None	N
H/L	0.1181	likely_benign	0.1168	benign	1.088	Stabilizing	0.001	N	0.143	neutral	N	0.466000906	None	None	N
H/M	0.3236	likely_benign	0.3353	benign	0.805	Stabilizing	0.893	D	0.314	neutral	None	None	None	None	N
H/N	0.0695	likely_benign	0.0708	benign	0.379	Stabilizing	0.425	N	0.253	neutral	N	0.428355555	None	None	N
H/P	0.1236	likely_benign	0.1127	benign	0.881	Stabilizing	0.784	D	0.412	neutral	N	0.465614651	None	None	N
H/Q	0.092	likely_benign	0.096	benign	0.472	Stabilizing	0.023	N	0.133	neutral	N	0.383724495	None	None	N
H/R	0.0665	likely_benign	0.0676	benign	-0.152	Destabilizing	0.002	N	0.126	neutral	N	0.409185689	None	None	N
H/S	0.1288	likely_benign	0.131	benign	0.423	Stabilizing	0.329	N	0.273	neutral	None	None	None	None	N
H/T	0.1381	likely_benign	0.138	benign	0.549	Stabilizing	0.013	N	0.131	neutral	None	None	None	None	N
H/V	0.2057	likely_benign	0.2098	benign	0.881	Stabilizing	0.329	N	0.341	neutral	None	None	None	None	N
H/W	0.3733	ambiguous	0.3828	ambiguous	1.021	Stabilizing	0.995	D	0.291	neutral	None	None	None	None	N
H/Y	0.1211	likely_benign	0.122	benign	1.312	Stabilizing	0.917	D	0.283	neutral	N	0.510569004	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.