TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7484	22675;22676;22677	chr2:178722337;178722336;178722335	chr2:179587064;179587063;179587062
N2AB	7167	21724;21725;21726	chr2:178722337;178722336;178722335	chr2:179587064;179587063;179587062
N2A	6240	18943;18944;18945	chr2:178722337;178722336;178722335	chr2:179587064;179587063;179587062
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-59
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.5392
• Predicted PPI site: I

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
S/I	None	None	0.965	N	0.361	0.548	0.726310685241	gnomAD-4.0.0	1.59273E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86074E-06	0	0
S/R	None	None	0.024	N	0.182	0.168	0.235664433957	gnomAD-4.0.0	1.59268E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86066E-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
S/A	0.0942	likely_benign	0.0921	benign	-0.234	Destabilizing	None	N	0.075	neutral	None	None	None	None	I
S/C	0.1641	likely_benign	0.1695	benign	-0.172	Destabilizing	0.994	D	0.336	neutral	D	0.543758665	None	None	I
S/D	0.2321	likely_benign	0.2273	benign	0.072	Stabilizing	0.583	D	0.199	neutral	None	None	None	None	I
S/E	0.3267	likely_benign	0.3059	benign	-0.038	Destabilizing	0.796	D	0.191	neutral	None	None	None	None	I
S/F	0.1887	likely_benign	0.18	benign	-0.936	Destabilizing	0.996	D	0.354	neutral	None	None	None	None	I
S/G	0.0784	likely_benign	0.0842	benign	-0.301	Destabilizing	0.447	N	0.283	neutral	N	0.519207599	None	None	I
S/H	0.1795	likely_benign	0.1846	benign	-0.717	Destabilizing	0.973	D	0.344	neutral	None	None	None	None	I
S/I	0.1315	likely_benign	0.1304	benign	-0.19	Destabilizing	0.965	D	0.361	neutral	N	0.507296666	None	None	I
S/K	0.3176	likely_benign	0.3073	benign	-0.364	Destabilizing	0.683	D	0.197	neutral	None	None	None	None	I
S/L	0.1164	likely_benign	0.112	benign	-0.19	Destabilizing	0.913	D	0.313	neutral	None	None	None	None	I
S/M	0.2075	likely_benign	0.2098	benign	0.002	Stabilizing	0.996	D	0.341	neutral	None	None	None	None	I
S/N	0.0915	likely_benign	0.0966	benign	-0.027	Destabilizing	None	N	0.092	neutral	N	0.487671474	None	None	I
S/P	0.3048	likely_benign	0.2853	benign	-0.179	Destabilizing	0.952	D	0.355	neutral	None	None	None	None	I
S/Q	0.2638	likely_benign	0.2597	benign	-0.291	Destabilizing	0.973	D	0.295	neutral	None	None	None	None	I
S/R	0.2259	likely_benign	0.2166	benign	-0.11	Destabilizing	0.024	N	0.182	neutral	N	0.513473706	None	None	I
S/T	0.0853	likely_benign	0.0824	benign	-0.15	Destabilizing	0.092	N	0.241	neutral	N	0.513455063	None	None	I
S/V	0.1778	likely_benign	0.1743	benign	-0.179	Destabilizing	0.662	D	0.313	neutral	None	None	None	None	I
S/W	0.2611	likely_benign	0.2463	benign	-0.993	Destabilizing	0.999	D	0.495	neutral	None	None	None	None	I
S/Y	0.179	likely_benign	0.1766	benign	-0.69	Destabilizing	0.996	D	0.353	neutral	None	None	None	None	I

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.