TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29985	90178;90179;90180	chr2:178552947;178552946;178552945	chr2:179417674;179417673;179417672
N2AB	28344	85255;85256;85257	chr2:178552947;178552946;178552945	chr2:179417674;179417673;179417672
N2A	27417	82474;82475;82476	chr2:178552947;178552946;178552945	chr2:179417674;179417673;179417672
N2B	20920	62983;62984;62985	chr2:178552947;178552946;178552945	chr2:179417674;179417673;179417672
Novex-1	21045	63358;63359;63360	chr2:178552947;178552946;178552945	chr2:179417674;179417673;179417672
Novex-2	21112	63559;63560;63561	chr2:178552947;178552946;178552945	chr2:179417674;179417673;179417672
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: Fn3-106
• Domain position: 53
• Structural Position: 70
• Q(SASA): 0.6783
• Predicted PPI site: I

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/Q	rs1327715051	None	0.241	N	0.17	0.104	0.275215494804	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
H/Q	rs1327715051	None	0.241	N	0.17	0.104	0.275215494804	gnomAD-4.0.0	1.3148E-05	None	None	None	None	I	None	4.82812E-05	0	None	0	0	None	0	0	0	0	0
H/Y	rs557248616	None	0.391	N	0.257	0.067	0.222439326576	gnomAD-4.0.0	1.20034E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31252E-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	0.1585	likely_benign	0.1369	benign	0.009	Stabilizing	0.001	N	0.086	neutral	None	None	None	None	I
H/C	0.1572	likely_benign	0.1368	benign	0.463	Stabilizing	0.901	D	0.239	neutral	None	None	None	None	I
H/D	0.1486	likely_benign	0.1279	benign	0.013	Stabilizing	0.028	N	0.221	neutral	N	0.333967988	None	None	I
H/E	0.1861	likely_benign	0.1588	benign	0.049	Stabilizing	0.07	N	0.129	neutral	None	None	None	None	I
H/F	0.3163	likely_benign	0.2947	benign	0.738	Stabilizing	0.46	N	0.323	neutral	None	None	None	None	I
H/G	0.1558	likely_benign	0.136	benign	-0.287	Destabilizing	0.016	N	0.198	neutral	None	None	None	None	I
H/I	0.3012	likely_benign	0.2773	benign	0.773	Stabilizing	0.174	N	0.352	neutral	None	None	None	None	I
H/K	0.172	likely_benign	0.1458	benign	-0.003	Destabilizing	0.148	N	0.225	neutral	None	None	None	None	I
H/L	0.1012	likely_benign	0.093	benign	0.773	Stabilizing	0.028	N	0.287	neutral	N	0.445210407	None	None	I
H/M	0.3486	ambiguous	0.3408	ambiguous	0.556	Stabilizing	0.749	D	0.231	neutral	None	None	None	None	I
H/N	0.0644	likely_benign	0.059	benign	0.016	Stabilizing	None	N	0.053	neutral	N	0.355882056	None	None	I
H/P	0.0893	likely_benign	0.0797	benign	0.544	Stabilizing	0.391	N	0.305	neutral	N	0.394728446	None	None	I
H/Q	0.1058	likely_benign	0.0928	benign	0.129	Stabilizing	0.241	N	0.17	neutral	N	0.395632523	None	None	I
H/R	0.0911	likely_benign	0.0785	benign	-0.506	Destabilizing	0.116	N	0.155	neutral	N	0.394765731	None	None	I
H/S	0.1055	likely_benign	0.0961	benign	0.02	Stabilizing	0.001	N	0.088	neutral	None	None	None	None	I
H/T	0.1321	likely_benign	0.1188	benign	0.158	Stabilizing	None	N	0.092	neutral	None	None	None	None	I
H/V	0.2061	likely_benign	0.1893	benign	0.544	Stabilizing	0.08	N	0.272	neutral	None	None	None	None	I
H/W	0.408	ambiguous	0.3953	ambiguous	0.816	Stabilizing	0.972	D	0.217	neutral	None	None	None	None	I
H/Y	0.1048	likely_benign	0.1009	benign	1.066	Stabilizing	0.391	N	0.257	neutral	N	0.429918455	None	None	I

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.