TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25604	77035;77036;77037	chr2:178569322;178569321;178569320	chr2:179434049;179434048;179434047
N2AB	23963	72112;72113;72114	chr2:178569322;178569321;178569320	chr2:179434049;179434048;179434047
N2A	23036	69331;69332;69333	chr2:178569322;178569321;178569320	chr2:179434049;179434048;179434047
N2B	16539	49840;49841;49842	chr2:178569322;178569321;178569320	chr2:179434049;179434048;179434047
Novex-1	16664	50215;50216;50217	chr2:178569322;178569321;178569320	chr2:179434049;179434048;179434047
Novex-2	16731	50416;50417;50418	chr2:178569322;178569321;178569320	chr2:179434049;179434048;179434047
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: Fn3-74
• Domain position: 4
• Structural Position: 4
• Q(SASA): 0.2561
• 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
P/L	rs1707251307	None	0.707	D	0.777	0.404	0.520694202979	gnomAD-4.0.0	2.0538E-06	None	None	None	None	I	None	0	0	None	0	0	None	1.87441E-05	0	1.79963E-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
P/A	0.0488	likely_benign	0.056	benign	-1.696	Destabilizing	0.001	N	0.437	neutral	N	0.443767612	None	None	I
P/C	0.353	ambiguous	0.4186	ambiguous	-1.089	Destabilizing	0.977	D	0.803	deleterious	None	None	None	None	I
P/D	0.6603	likely_pathogenic	0.7285	pathogenic	-1.891	Destabilizing	0.059	N	0.707	prob.neutral	None	None	None	None	I
P/E	0.2972	likely_benign	0.3656	ambiguous	-1.883	Destabilizing	0.001	N	0.45	neutral	None	None	None	None	I
P/F	0.5293	ambiguous	0.6104	pathogenic	-1.322	Destabilizing	0.957	D	0.816	deleterious	None	None	None	None	I
P/G	0.3042	likely_benign	0.3551	ambiguous	-2.019	Highly Destabilizing	0.392	N	0.748	deleterious	None	None	None	None	I
P/H	0.2449	likely_benign	0.3036	benign	-1.566	Destabilizing	0.985	D	0.788	deleterious	None	None	None	None	I
P/I	0.3843	ambiguous	0.4532	ambiguous	-0.89	Destabilizing	0.918	D	0.809	deleterious	None	None	None	None	I
P/K	0.3541	ambiguous	0.4587	ambiguous	-1.348	Destabilizing	0.761	D	0.685	prob.neutral	None	None	None	None	I
P/L	0.163	likely_benign	0.2143	benign	-0.89	Destabilizing	0.707	D	0.777	deleterious	D	0.53961243	None	None	I
P/M	0.3117	likely_benign	0.3886	ambiguous	-0.66	Destabilizing	0.33	N	0.615	neutral	None	None	None	None	I
P/N	0.4567	ambiguous	0.5207	ambiguous	-1.168	Destabilizing	0.736	D	0.781	deleterious	None	None	None	None	I
P/Q	0.1571	likely_benign	0.2024	benign	-1.369	Destabilizing	0.76	D	0.725	prob.delet.	D	0.526481698	None	None	I
P/R	0.2336	likely_benign	0.3237	benign	-0.807	Destabilizing	0.034	N	0.522	neutral	N	0.502136473	None	None	I
P/S	0.1036	likely_benign	0.1179	benign	-1.654	Destabilizing	0.402	N	0.681	prob.neutral	N	0.496603064	None	None	I
P/T	0.1448	likely_benign	0.172	benign	-1.55	Destabilizing	0.374	N	0.701	prob.neutral	N	0.509644891	None	None	I
P/V	0.23	likely_benign	0.2909	benign	-1.126	Destabilizing	0.359	N	0.755	deleterious	None	None	None	None	I
P/W	0.7561	likely_pathogenic	0.833	pathogenic	-1.543	Destabilizing	0.998	D	0.812	deleterious	None	None	None	None	I
P/Y	0.5076	ambiguous	0.5929	pathogenic	-1.264	Destabilizing	0.993	D	0.819	deleterious	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.