TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	6675	20248;20249;20250	chr2:178727342;178727341;178727340	chr2:179592069;179592068;179592067
N2AB	6358	19297;19298;19299	chr2:178727342;178727341;178727340	chr2:179592069;179592068;179592067
N2A	5431	16516;16517;16518	chr2:178727342;178727341;178727340	chr2:179592069;179592068;179592067
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: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Ig-51
• Domain position: 9
• Structural Position: 11
• Q(SASA): 0.5999
• 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
A/D	None	None	0.901	N	0.518	0.182	0.215869574891	gnomAD-4.0.0	6.89045E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.03599E-07	0	0
A/V	rs778363589	0.066	0.008	N	0.207	0.096	0.141422826196	gnomAD-2.1.1	4.14E-06	None	None	None	None	I	None	0	3.01E-05	None	0	0	None	0	None	0	0	0
A/V	rs778363589	0.066	0.008	N	0.207	0.096	0.141422826196	gnomAD-4.0.0	6.89045E-07	None	None	None	None	I	None	0	2.30563E-05	None	0	0	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
A/C	0.6642	likely_pathogenic	0.6959	pathogenic	-0.72	Destabilizing	0.996	D	0.366	neutral	None	None	None	None	I
A/D	0.2739	likely_benign	0.3634	ambiguous	-0.364	Destabilizing	0.901	D	0.518	neutral	N	0.398810822	None	None	I
A/E	0.2926	likely_benign	0.3792	ambiguous	-0.525	Destabilizing	0.923	D	0.381	neutral	None	None	None	None	I
A/F	0.3906	ambiguous	0.3966	ambiguous	-0.856	Destabilizing	0.923	D	0.561	neutral	None	None	None	None	I
A/G	0.1241	likely_benign	0.1266	benign	-0.136	Destabilizing	0.722	D	0.308	neutral	N	0.43496641	None	None	I
A/H	0.4993	ambiguous	0.5485	ambiguous	-0.218	Destabilizing	0.996	D	0.557	neutral	None	None	None	None	I
A/I	0.271	likely_benign	0.2594	benign	-0.302	Destabilizing	0.372	N	0.424	neutral	None	None	None	None	I
A/K	0.5467	ambiguous	0.6351	pathogenic	-0.396	Destabilizing	0.923	D	0.376	neutral	None	None	None	None	I
A/L	0.1904	likely_benign	0.1893	benign	-0.302	Destabilizing	0.633	D	0.373	neutral	None	None	None	None	I
A/M	0.255	likely_benign	0.2469	benign	-0.352	Destabilizing	0.979	D	0.443	neutral	None	None	None	None	I
A/N	0.192	likely_benign	0.2077	benign	-0.116	Destabilizing	0.923	D	0.547	neutral	None	None	None	None	I
A/P	0.0943	likely_benign	0.0996	benign	-0.215	Destabilizing	0.018	N	0.225	neutral	N	0.366837263	None	None	I
A/Q	0.3532	ambiguous	0.3944	ambiguous	-0.395	Destabilizing	0.961	D	0.431	neutral	None	None	None	None	I
A/R	0.5202	ambiguous	0.6068	pathogenic	0.013	Stabilizing	0.961	D	0.427	neutral	None	None	None	None	I
A/S	0.0883	likely_benign	0.0909	benign	-0.293	Destabilizing	0.565	D	0.383	neutral	N	0.371915009	None	None	I
A/T	0.0887	likely_benign	0.0912	benign	-0.379	Destabilizing	0.034	N	0.203	neutral	N	0.409299961	None	None	I
A/V	0.1374	likely_benign	0.1332	benign	-0.215	Destabilizing	0.008	N	0.207	neutral	N	0.482181567	None	None	I
A/W	0.7822	likely_pathogenic	0.8132	pathogenic	-0.977	Destabilizing	0.996	D	0.642	neutral	None	None	None	None	I
A/Y	0.4952	ambiguous	0.5312	ambiguous	-0.625	Destabilizing	0.961	D	0.563	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.