TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23468	70627;70628;70629	chr2:178575730;178575729;178575728	chr2:179440457;179440456;179440455
N2AB	21827	65704;65705;65706	chr2:178575730;178575729;178575728	chr2:179440457;179440456;179440455
N2A	20900	62923;62924;62925	chr2:178575730;178575729;178575728	chr2:179440457;179440456;179440455
N2B	14403	43432;43433;43434	chr2:178575730;178575729;178575728	chr2:179440457;179440456;179440455
Novex-1	14528	43807;43808;43809	chr2:178575730;178575729;178575728	chr2:179440457;179440456;179440455
Novex-2	14595	44008;44009;44010	chr2:178575730;178575729;178575728	chr2:179440457;179440456;179440455
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACA
• RefSeq wild type template codon: TGT
• Domain: Fn3-58
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.4427
• 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
T/K	None	None	0.134	N	0.21	0.252	0.266843984389	gnomAD-4.0.0	1.59179E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85919E-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	0.1411	likely_benign	0.1308	benign	-0.645	Destabilizing	0.826	D	0.374	neutral	N	0.481741266	None	None	I
T/C	0.4597	ambiguous	0.4366	ambiguous	-0.259	Destabilizing	0.1	N	0.238	neutral	None	None	None	None	I
T/D	0.7038	likely_pathogenic	0.6714	pathogenic	-0.514	Destabilizing	0.969	D	0.379	neutral	None	None	None	None	I
T/E	0.5449	ambiguous	0.5124	ambiguous	-0.535	Destabilizing	0.939	D	0.347	neutral	None	None	None	None	I
T/F	0.3999	ambiguous	0.3729	ambiguous	-0.727	Destabilizing	0.991	D	0.42	neutral	None	None	None	None	I
T/G	0.3187	likely_benign	0.2981	benign	-0.889	Destabilizing	0.969	D	0.366	neutral	None	None	None	None	I
T/H	0.2949	likely_benign	0.2878	benign	-1.214	Destabilizing	0.1	N	0.28	neutral	None	None	None	None	I
T/I	0.219	likely_benign	0.1954	benign	-0.087	Destabilizing	0.988	D	0.43	neutral	N	0.487622751	None	None	I
T/K	0.2692	likely_benign	0.2555	benign	-0.846	Destabilizing	0.134	N	0.21	neutral	N	0.455144973	None	None	I
T/L	0.1274	likely_benign	0.1125	benign	-0.087	Destabilizing	0.939	D	0.359	neutral	None	None	None	None	I
T/M	0.1211	likely_benign	0.1087	benign	0.293	Stabilizing	0.997	D	0.413	neutral	None	None	None	None	I
T/N	0.1664	likely_benign	0.1538	benign	-0.675	Destabilizing	0.939	D	0.24	neutral	None	None	None	None	I
T/P	0.686	likely_pathogenic	0.6738	pathogenic	-0.241	Destabilizing	0.996	D	0.441	neutral	N	0.521370044	None	None	I
T/Q	0.2863	likely_benign	0.2662	benign	-0.873	Destabilizing	0.982	D	0.43	neutral	None	None	None	None	I
T/R	0.2581	likely_benign	0.2536	benign	-0.543	Destabilizing	0.035	N	0.199	neutral	N	0.514923995	None	None	I
T/S	0.1361	likely_benign	0.1248	benign	-0.856	Destabilizing	0.826	D	0.311	neutral	N	0.458838639	None	None	I
T/V	0.1753	likely_benign	0.1604	benign	-0.241	Destabilizing	0.939	D	0.242	neutral	None	None	None	None	I
T/W	0.7571	likely_pathogenic	0.7363	pathogenic	-0.712	Destabilizing	0.999	D	0.423	neutral	None	None	None	None	I
T/Y	0.4451	ambiguous	0.4179	ambiguous	-0.499	Destabilizing	0.982	D	0.44	neutral	None	None	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.