TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19636	59131;59132;59133	chr2:178593302;178593301;178593300	chr2:179458029;179458028;179458027
N2AB	17995	54208;54209;54210	chr2:178593302;178593301;178593300	chr2:179458029;179458028;179458027
N2A	17068	51427;51428;51429	chr2:178593302;178593301;178593300	chr2:179458029;179458028;179458027
N2B	10571	31936;31937;31938	chr2:178593302;178593301;178593300	chr2:179458029;179458028;179458027
Novex-1	10696	32311;32312;32313	chr2:178593302;178593301;178593300	chr2:179458029;179458028;179458027
Novex-2	10763	32512;32513;32514	chr2:178593302;178593301;178593300	chr2:179458029;179458028;179458027
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-30
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.6207
• 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
Y/C	None	None	0.873	N	0.563	0.224	0.462374447365	gnomAD-4.0.0	1.592E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85964E-06	0	0
Y/H	None	None	0.001	N	0.227	0.089	0.149567049428	gnomAD-4.0.0	1.20034E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.31253E-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
Y/A	0.1378	likely_benign	0.1734	benign	-1.081	Destabilizing	0.036	N	0.297	neutral	None	None	None	None	N
Y/C	0.0898	likely_benign	0.0923	benign	-0.169	Destabilizing	0.873	D	0.563	neutral	N	0.45327253	None	None	N
Y/D	0.0917	likely_benign	0.1062	benign	0.127	Stabilizing	None	N	0.378	neutral	N	0.32367085	None	None	N
Y/E	0.2184	likely_benign	0.277	benign	0.143	Stabilizing	0.036	N	0.293	neutral	None	None	None	None	N
Y/F	0.0756	likely_benign	0.0816	benign	-0.447	Destabilizing	0.391	N	0.431	neutral	N	0.443863613	None	None	N
Y/G	0.1594	likely_benign	0.1791	benign	-1.312	Destabilizing	None	N	0.391	neutral	None	None	None	None	N
Y/H	0.0963	likely_benign	0.1084	benign	-0.146	Destabilizing	0.001	N	0.227	neutral	N	0.421680187	None	None	N
Y/I	0.2312	likely_benign	0.2789	benign	-0.446	Destabilizing	0.46	N	0.46	neutral	None	None	None	None	N
Y/K	0.2968	likely_benign	0.3468	ambiguous	-0.355	Destabilizing	0.001	N	0.302	neutral	None	None	None	None	N
Y/L	0.2079	likely_benign	0.2528	benign	-0.446	Destabilizing	0.148	N	0.303	neutral	None	None	None	None	N
Y/M	0.3061	likely_benign	0.3737	ambiguous	-0.352	Destabilizing	0.901	D	0.495	neutral	None	None	None	None	N
Y/N	0.0608	likely_benign	0.0747	benign	-0.648	Destabilizing	0.002	N	0.319	neutral	N	0.369904572	None	None	N
Y/P	0.4381	ambiguous	0.4856	ambiguous	-0.643	Destabilizing	0.46	N	0.473	neutral	None	None	None	None	N
Y/Q	0.1828	likely_benign	0.2312	benign	-0.561	Destabilizing	0.148	N	0.395	neutral	None	None	None	None	N
Y/R	0.2279	likely_benign	0.2621	benign	-0.098	Destabilizing	0.08	N	0.385	neutral	None	None	None	None	N
Y/S	0.0728	likely_benign	0.0859	benign	-0.985	Destabilizing	0.002	N	0.331	neutral	N	0.352145531	None	None	N
Y/T	0.1473	likely_benign	0.1849	benign	-0.877	Destabilizing	0.08	N	0.274	neutral	None	None	None	None	N
Y/V	0.1645	likely_benign	0.192	benign	-0.643	Destabilizing	0.148	N	0.371	neutral	None	None	None	None	N
Y/W	0.3554	ambiguous	0.3651	ambiguous	-0.454	Destabilizing	0.901	D	0.489	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.