TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14934	45025;45026;45027	chr2:178624480;178624479;178624478	chr2:179489207;179489206;179489205
N2AB	13293	40102;40103;40104	chr2:178624480;178624479;178624478	chr2:179489207;179489206;179489205
N2A	12366	37321;37322;37323	chr2:178624480;178624479;178624478	chr2:179489207;179489206;179489205
N2B	5869	17830;17831;17832	chr2:178624480;178624479;178624478	chr2:179489207;179489206;179489205
Novex-1	5994	18205;18206;18207	chr2:178624480;178624479;178624478	chr2:179489207;179489206;179489205
Novex-2	6061	18406;18407;18408	chr2:178624480;178624479;178624478	chr2:179489207;179489206;179489205
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-100
• Domain position: 82
• Structural Position: 168
• Q(SASA): 0.583
• 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
N/K	None	None	0.491	N	0.353	0.151	0.0716867268079	gnomAD-4.0.0	6.84769E-07	None	None	None	None	N	None	0	0	None	0	2.52449E-05	None	0	0	0	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
N/A	0.2984	likely_benign	0.2584	benign	-0.577	Destabilizing	0.103	N	0.266	neutral	None	None	None	None	N
N/C	0.3759	ambiguous	0.3102	benign	0.205	Stabilizing	0.965	D	0.475	neutral	None	None	None	None	N
N/D	0.195	likely_benign	0.2018	benign	-0.905	Destabilizing	0.285	N	0.37	neutral	N	0.346015498	None	None	N
N/E	0.4083	ambiguous	0.4477	ambiguous	-0.889	Destabilizing	0.345	N	0.358	neutral	None	None	None	None	N
N/F	0.3328	likely_benign	0.3287	benign	-0.766	Destabilizing	0.001	N	0.315	neutral	None	None	None	None	N
N/G	0.459	ambiguous	0.4211	ambiguous	-0.826	Destabilizing	0.345	N	0.274	neutral	None	None	None	None	N
N/H	0.089	likely_benign	0.0825	benign	-0.863	Destabilizing	0.954	D	0.472	neutral	N	0.352110544	None	None	N
N/I	0.1687	likely_benign	0.1592	benign	0.016	Stabilizing	0.326	N	0.464	neutral	N	0.341746414	None	None	N
N/K	0.2716	likely_benign	0.3201	benign	-0.146	Destabilizing	0.491	N	0.353	neutral	N	0.31249357	None	None	N
N/L	0.2217	likely_benign	0.1988	benign	0.016	Stabilizing	0.209	N	0.29	neutral	None	None	None	None	N
N/M	0.3452	ambiguous	0.2998	benign	0.674	Stabilizing	0.901	D	0.485	neutral	None	None	None	None	N
N/P	0.7352	likely_pathogenic	0.7674	pathogenic	-0.154	Destabilizing	0.722	D	0.534	neutral	None	None	None	None	N
N/Q	0.3169	likely_benign	0.3234	benign	-0.902	Destabilizing	0.722	D	0.467	neutral	None	None	None	None	N
N/R	0.2758	likely_benign	0.3326	benign	-0.011	Destabilizing	0.561	D	0.442	neutral	None	None	None	None	N
N/S	0.1078	likely_benign	0.0877	benign	-0.555	Destabilizing	0.016	N	0.198	neutral	N	0.346513697	None	None	N
N/T	0.1432	likely_benign	0.1298	benign	-0.385	Destabilizing	0.001	N	0.191	neutral	N	0.346769061	None	None	N
N/V	0.2183	likely_benign	0.1859	benign	-0.154	Destabilizing	0.209	N	0.395	neutral	None	None	None	None	N
N/W	0.7169	likely_pathogenic	0.7004	pathogenic	-0.636	Destabilizing	0.991	D	0.475	neutral	None	None	None	None	N
N/Y	0.1209	likely_benign	0.1082	benign	-0.376	Destabilizing	0.326	N	0.464	neutral	N	0.34892411	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.