TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19770	59533;59534;59535	chr2:178592811;178592810;178592809	chr2:179457538;179457537;179457536
N2AB	18129	54610;54611;54612	chr2:178592811;178592810;178592809	chr2:179457538;179457537;179457536
N2A	17202	51829;51830;51831	chr2:178592811;178592810;178592809	chr2:179457538;179457537;179457536
N2B	10705	32338;32339;32340	chr2:178592811;178592810;178592809	chr2:179457538;179457537;179457536
Novex-1	10830	32713;32714;32715	chr2:178592811;178592810;178592809	chr2:179457538;179457537;179457536
Novex-2	10897	32914;32915;32916	chr2:178592811;178592810;178592809	chr2:179457538;179457537;179457536
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: H
• RefSeq wild type transcript codon: CAT
• RefSeq wild type template codon: GTA
• Domain: Fn3-31
• Domain position: 91
• Structural Position: 122
• Q(SASA): 0.7957
• 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
H/R	rs762714656	-0.337	0.026	N	0.319	0.118	0.170165803431	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
H/R	rs762714656	-0.337	0.026	N	0.319	0.118	0.170165803431	gnomAD-4.0.0	1.59194E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85943E-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	0.1251	likely_benign	0.1439	benign	-0.922	Destabilizing	0.003	N	0.28	neutral	None	None	None	None	N
H/C	0.0995	likely_benign	0.1019	benign	-0.047	Destabilizing	0.439	N	0.42	neutral	None	None	None	None	N
H/D	0.1149	likely_benign	0.1276	benign	-1.093	Destabilizing	0.006	N	0.29	neutral	N	0.34895051	None	None	N
H/E	0.1544	likely_benign	0.1631	benign	-0.954	Destabilizing	0.007	N	0.307	neutral	None	None	None	None	N
H/F	0.1228	likely_benign	0.1284	benign	0.686	Stabilizing	0.007	N	0.325	neutral	None	None	None	None	N
H/G	0.2146	likely_benign	0.2411	benign	-1.316	Destabilizing	0.003	N	0.287	neutral	None	None	None	None	N
H/I	0.1373	likely_benign	0.1422	benign	0.196	Stabilizing	0.035	N	0.545	neutral	None	None	None	None	N
H/K	0.2021	likely_benign	0.2167	benign	-0.558	Destabilizing	0.007	N	0.287	neutral	None	None	None	None	N
H/L	0.0816	likely_benign	0.0826	benign	0.196	Stabilizing	0.006	N	0.303	neutral	N	0.392416072	None	None	N
H/M	0.2179	likely_benign	0.2447	benign	-0.03	Destabilizing	0.204	N	0.469	neutral	None	None	None	None	N
H/N	0.0652	likely_benign	0.0736	benign	-0.988	Destabilizing	None	N	0.139	neutral	N	0.380697569	None	None	N
H/P	0.0969	likely_benign	0.1085	benign	-0.16	Destabilizing	0.052	N	0.566	neutral	N	0.358802144	None	None	N
H/Q	0.1198	likely_benign	0.1294	benign	-0.708	Destabilizing	0.026	N	0.339	neutral	N	0.376465185	None	None	N
H/R	0.1205	likely_benign	0.1207	benign	-1.077	Destabilizing	0.026	N	0.319	neutral	N	0.385604743	None	None	N
H/S	0.1089	likely_benign	0.1227	benign	-0.908	Destabilizing	0.001	N	0.221	neutral	None	None	None	None	N
H/T	0.1209	likely_benign	0.1347	benign	-0.656	Destabilizing	0.007	N	0.314	neutral	None	None	None	None	N
H/V	0.1056	likely_benign	0.1132	benign	-0.16	Destabilizing	0.015	N	0.371	neutral	None	None	None	None	N
H/W	0.2341	likely_benign	0.2449	benign	1.107	Stabilizing	0.204	N	0.458	neutral	None	None	None	None	N
H/Y	0.0537	likely_benign	0.0555	benign	1.021	Stabilizing	None	N	0.105	neutral	N	0.356668703	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.