TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17162	51709;51710;51711	chr2:178609939;178609938;178609937	chr2:179474666;179474665;179474664
N2AB	15521	46786;46787;46788	chr2:178609939;178609938;178609937	chr2:179474666;179474665;179474664
N2A	14594	44005;44006;44007	chr2:178609939;178609938;178609937	chr2:179474666;179474665;179474664
N2B	8097	24514;24515;24516	chr2:178609939;178609938;178609937	chr2:179474666;179474665;179474664
Novex-1	8222	24889;24890;24891	chr2:178609939;178609938;178609937	chr2:179474666;179474665;179474664
Novex-2	8289	25090;25091;25092	chr2:178609939;178609938;178609937	chr2:179474666;179474665;179474664
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: E
• RefSeq wild type transcript codon: GAG
• RefSeq wild type template codon: CTC
• Domain: Fn3-13
• Domain position: 16
• Structural Position: 18
• Q(SASA): 0.4781
• 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
E/G	None	None	0.012	N	0.259	0.101	0.254761474806	gnomAD-4.0.0	1.59316E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86195E-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
E/A	0.105	likely_benign	0.1024	benign	-0.681	Destabilizing	0.005	N	0.235	neutral	N	0.486465171	None	None	N
E/C	0.6955	likely_pathogenic	0.6734	pathogenic	-0.042	Destabilizing	0.864	D	0.258	neutral	None	None	None	None	N
E/D	0.115	likely_benign	0.1125	benign	-0.582	Destabilizing	0.012	N	0.235	neutral	N	0.394053655	None	None	N
E/F	0.6539	likely_pathogenic	0.6338	pathogenic	-0.601	Destabilizing	0.628	D	0.304	neutral	None	None	None	None	N
E/G	0.1192	likely_benign	0.1113	benign	-0.92	Destabilizing	0.012	N	0.259	neutral	N	0.458374492	None	None	N
E/H	0.2636	likely_benign	0.2597	benign	-0.695	Destabilizing	0.214	N	0.312	neutral	None	None	None	None	N
E/I	0.3188	likely_benign	0.3139	benign	-0.067	Destabilizing	0.356	N	0.378	neutral	None	None	None	None	N
E/K	0.0726	likely_benign	0.0717	benign	0.078	Stabilizing	None	N	0.056	neutral	N	0.442578321	None	None	N
E/L	0.2839	likely_benign	0.2727	benign	-0.067	Destabilizing	0.072	N	0.361	neutral	None	None	None	None	N
E/M	0.312	likely_benign	0.308	benign	0.313	Stabilizing	0.628	D	0.279	neutral	None	None	None	None	N
E/N	0.1321	likely_benign	0.1354	benign	-0.231	Destabilizing	None	N	0.067	neutral	None	None	None	None	N
E/P	0.8182	likely_pathogenic	0.7675	pathogenic	-0.251	Destabilizing	0.136	N	0.405	neutral	None	None	None	None	N
E/Q	0.089	likely_benign	0.0894	benign	-0.203	Destabilizing	0.029	N	0.257	neutral	N	0.475421458	None	None	N
E/R	0.1339	likely_benign	0.1285	benign	0.181	Stabilizing	0.016	N	0.215	neutral	None	None	None	None	N
E/S	0.1114	likely_benign	0.1126	benign	-0.434	Destabilizing	0.001	N	0.083	neutral	None	None	None	None	N
E/T	0.1169	likely_benign	0.1179	benign	-0.24	Destabilizing	0.016	N	0.321	neutral	None	None	None	None	N
E/V	0.2012	likely_benign	0.1933	benign	-0.251	Destabilizing	0.055	N	0.364	neutral	N	0.518961591	None	None	N
E/W	0.823	likely_pathogenic	0.7967	pathogenic	-0.429	Destabilizing	0.864	D	0.301	neutral	None	None	None	None	N
E/Y	0.4872	ambiguous	0.4581	ambiguous	-0.354	Destabilizing	0.628	D	0.297	neutral	None	None	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.