TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	25533	76822;76823;76824	chr2:178569535;178569534;178569533	chr2:179434262;179434261;179434260
N2AB	23892	71899;71900;71901	chr2:178569535;178569534;178569533	chr2:179434262;179434261;179434260
N2A	22965	69118;69119;69120	chr2:178569535;178569534;178569533	chr2:179434262;179434261;179434260
N2B	16468	49627;49628;49629	chr2:178569535;178569534;178569533	chr2:179434262;179434261;179434260
Novex-1	16593	50002;50003;50004	chr2:178569535;178569534;178569533	chr2:179434262;179434261;179434260
Novex-2	16660	50203;50204;50205	chr2:178569535;178569534;178569533	chr2:179434262;179434261;179434260
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-135
• Domain position: 20
• Structural Position: 34
• Q(SASA): 0.2871
• 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/S	rs1707347772	None	1.0	D	0.78	0.426	0.448300063881	gnomAD-4.0.0	3.60097E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.9375E-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	0.1709	likely_benign	0.2141	benign	-0.97	Destabilizing	1.0	D	0.74	deleterious	D	0.525976069	None	None	I
P/C	0.7798	likely_pathogenic	0.8341	pathogenic	-0.749	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	I
P/D	0.8759	likely_pathogenic	0.8954	pathogenic	-0.687	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
P/E	0.7461	likely_pathogenic	0.7826	pathogenic	-0.664	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
P/F	0.8547	likely_pathogenic	0.8983	pathogenic	-0.659	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
P/G	0.601	likely_pathogenic	0.6363	pathogenic	-1.258	Destabilizing	1.0	D	0.761	deleterious	None	None	None	None	I
P/H	0.5435	ambiguous	0.5996	pathogenic	-0.59	Destabilizing	1.0	D	0.741	deleterious	N	0.496706694	None	None	I
P/I	0.6545	likely_pathogenic	0.7428	pathogenic	-0.285	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	I
P/K	0.717	likely_pathogenic	0.7411	pathogenic	-0.79	Destabilizing	1.0	D	0.769	deleterious	None	None	None	None	I
P/L	0.2877	likely_benign	0.3458	ambiguous	-0.285	Destabilizing	1.0	D	0.764	deleterious	N	0.487743472	None	None	I
P/M	0.5922	likely_pathogenic	0.6569	pathogenic	-0.426	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
P/N	0.6683	likely_pathogenic	0.71	pathogenic	-0.795	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
P/Q	0.4634	ambiguous	0.5205	ambiguous	-0.874	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
P/R	0.5566	ambiguous	0.5964	pathogenic	-0.351	Destabilizing	1.0	D	0.775	deleterious	D	0.523917199	None	None	I
P/S	0.3013	likely_benign	0.3639	ambiguous	-1.275	Destabilizing	1.0	D	0.78	deleterious	D	0.530112453	None	None	I
P/T	0.2082	likely_benign	0.2565	benign	-1.132	Destabilizing	1.0	D	0.773	deleterious	N	0.477470046	None	None	I
P/V	0.4653	ambiguous	0.5597	ambiguous	-0.479	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	I
P/W	0.9321	likely_pathogenic	0.9502	pathogenic	-0.858	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/Y	0.8202	likely_pathogenic	0.8697	pathogenic	-0.52	Destabilizing	1.0	D	0.755	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.