TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30002	90229;90230;90231	chr2:178552896;178552895;178552894	chr2:179417623;179417622;179417621
N2AB	28361	85306;85307;85308	chr2:178552896;178552895;178552894	chr2:179417623;179417622;179417621
N2A	27434	82525;82526;82527	chr2:178552896;178552895;178552894	chr2:179417623;179417622;179417621
N2B	20937	63034;63035;63036	chr2:178552896;178552895;178552894	chr2:179417623;179417622;179417621
Novex-1	21062	63409;63410;63411	chr2:178552896;178552895;178552894	chr2:179417623;179417622;179417621
Novex-2	21129	63610;63611;63612	chr2:178552896;178552895;178552894	chr2:179417623;179417622;179417621
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-106
• Domain position: 70
• Structural Position: 103
• Q(SASA): 0.2399
• 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
P/T	None	None	0.454	N	0.379	0.182	0.236890367714	gnomAD-4.0.0	1.59126E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-05	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
P/A	0.0744	likely_benign	0.0718	benign	-1.595	Destabilizing	0.002	N	0.225	neutral	N	0.410351259	None	None	N
P/C	0.5056	ambiguous	0.4533	ambiguous	-0.914	Destabilizing	0.991	D	0.599	neutral	None	None	None	None	N
P/D	0.6279	likely_pathogenic	0.6255	pathogenic	-1.381	Destabilizing	0.842	D	0.437	neutral	None	None	None	None	N
P/E	0.4592	ambiguous	0.4565	ambiguous	-1.336	Destabilizing	0.842	D	0.435	neutral	None	None	None	None	N
P/F	0.6146	likely_pathogenic	0.577	pathogenic	-1.172	Destabilizing	0.974	D	0.588	neutral	None	None	None	None	N
P/G	0.3755	ambiguous	0.3552	ambiguous	-1.966	Destabilizing	0.525	D	0.394	neutral	None	None	None	None	N
P/H	0.3133	likely_benign	0.2956	benign	-1.565	Destabilizing	0.991	D	0.579	neutral	None	None	None	None	N
P/I	0.3277	likely_benign	0.3066	benign	-0.652	Destabilizing	0.842	D	0.568	neutral	None	None	None	None	N
P/K	0.5818	likely_pathogenic	0.5654	pathogenic	-1.111	Destabilizing	0.842	D	0.429	neutral	None	None	None	None	N
P/L	0.1579	likely_benign	0.1438	benign	-0.652	Destabilizing	0.801	D	0.493	neutral	N	0.403251928	None	None	N
P/M	0.3711	ambiguous	0.3443	ambiguous	-0.433	Destabilizing	0.991	D	0.583	neutral	None	None	None	None	N
P/N	0.3864	ambiguous	0.3702	ambiguous	-0.952	Destabilizing	0.842	D	0.511	neutral	None	None	None	None	N
P/Q	0.2664	likely_benign	0.2564	benign	-1.064	Destabilizing	0.966	D	0.495	neutral	N	0.392957577	None	None	N
P/R	0.4113	ambiguous	0.3915	ambiguous	-0.71	Destabilizing	0.934	D	0.543	neutral	N	0.402366494	None	None	N
P/S	0.1278	likely_benign	0.1233	benign	-1.55	Destabilizing	0.022	N	0.225	neutral	N	0.335661499	None	None	N
P/T	0.1171	likely_benign	0.113	benign	-1.391	Destabilizing	0.454	N	0.379	neutral	N	0.363058744	None	None	N
P/V	0.2177	likely_benign	0.2002	benign	-0.933	Destabilizing	0.728	D	0.475	neutral	None	None	None	None	N
P/W	0.7772	likely_pathogenic	0.7484	pathogenic	-1.446	Destabilizing	0.998	D	0.63	neutral	None	None	None	None	N
P/Y	0.504	ambiguous	0.4744	ambiguous	-1.119	Destabilizing	0.991	D	0.602	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.