TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35213	105862;105863;105864	chr2:178530978;178530977;178530976	chr2:179395705;179395704;179395703
N2AB	33572	100939;100940;100941	chr2:178530978;178530977;178530976	chr2:179395705;179395704;179395703
N2A	32645	98158;98159;98160	chr2:178530978;178530977;178530976	chr2:179395705;179395704;179395703
N2B	26148	78667;78668;78669	chr2:178530978;178530977;178530976	chr2:179395705;179395704;179395703
Novex-1	26273	79042;79043;79044	chr2:178530978;178530977;178530976	chr2:179395705;179395704;179395703
Novex-2	26340	79243;79244;79245	chr2:178530978;178530977;178530976	chr2:179395705;179395704;179395703
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: Ig-164
• Domain position: 85
• Structural Position: 171
• Q(SASA): 0.2786
• 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/A	rs748652325	-1.233	None	N	0.206	0.127	0.291694819147	gnomAD-2.1.1	8.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.54E-05	None	0	0	0
E/A	rs748652325	-1.233	None	N	0.206	0.127	0.291694819147	gnomAD-4.0.0	4.10482E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.69817E-06	3.47794E-05	0
E/K	None	None	None	N	0.164	0.099	0.184867976434	gnomAD-4.0.0	3.18176E-06	None	None	None	None	N	None	0	0	None	0	5.54477E-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
E/A	0.1104	likely_benign	0.1116	benign	-0.538	Destabilizing	None	N	0.206	neutral	N	0.465026398	None	None	N
E/C	0.7078	likely_pathogenic	0.725	pathogenic	-0.081	Destabilizing	0.116	N	0.589	neutral	None	None	None	None	N
E/D	0.1772	likely_benign	0.1641	benign	-0.481	Destabilizing	0.001	N	0.172	neutral	N	0.444285766	None	None	N
E/F	0.594	likely_pathogenic	0.5962	pathogenic	-0.366	Destabilizing	0.008	N	0.388	neutral	None	None	None	None	N
E/G	0.1398	likely_benign	0.1459	benign	-0.769	Destabilizing	0.001	N	0.298	neutral	N	0.515185859	None	None	N
E/H	0.2249	likely_benign	0.2037	benign	-0.273	Destabilizing	None	N	0.129	neutral	None	None	None	None	N
E/I	0.2624	likely_benign	0.2569	benign	0.051	Stabilizing	0.008	N	0.371	neutral	None	None	None	None	N
E/K	0.0954	likely_benign	0.0926	benign	0.138	Stabilizing	None	N	0.164	neutral	N	0.49732803	None	None	N
E/L	0.2095	likely_benign	0.1997	benign	0.051	Stabilizing	0.001	N	0.364	neutral	None	None	None	None	N
E/M	0.3303	likely_benign	0.3298	benign	0.254	Stabilizing	0.041	N	0.504	neutral	None	None	None	None	N
E/N	0.1878	likely_benign	0.1744	benign	-0.167	Destabilizing	0.002	N	0.209	neutral	None	None	None	None	N
E/P	0.3821	ambiguous	0.3354	benign	-0.125	Destabilizing	0.003	N	0.321	neutral	None	None	None	None	N
E/Q	0.0661	likely_benign	0.0626	benign	-0.132	Destabilizing	None	N	0.101	neutral	N	0.491674282	None	None	N
E/R	0.1347	likely_benign	0.1316	benign	0.359	Stabilizing	0.001	N	0.209	neutral	None	None	None	None	N
E/S	0.1385	likely_benign	0.1336	benign	-0.366	Destabilizing	None	N	0.164	neutral	None	None	None	None	N
E/T	0.1324	likely_benign	0.1275	benign	-0.181	Destabilizing	0.001	N	0.247	neutral	None	None	None	None	N
E/V	0.171	likely_benign	0.1682	benign	-0.125	Destabilizing	0.001	N	0.321	neutral	N	0.495157304	None	None	N
E/W	0.7039	likely_pathogenic	0.7045	pathogenic	-0.182	Destabilizing	0.316	N	0.544	neutral	None	None	None	None	N
E/Y	0.4259	ambiguous	0.4149	ambiguous	-0.116	Destabilizing	0.002	N	0.401	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.