TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17106	51541;51542;51543	chr2:178610210;178610209;178610208	chr2:179474937;179474936;179474935
N2AB	15465	46618;46619;46620	chr2:178610210;178610209;178610208	chr2:179474937;179474936;179474935
N2A	14538	43837;43838;43839	chr2:178610210;178610209;178610208	chr2:179474937;179474936;179474935
N2B	8041	24346;24347;24348	chr2:178610210;178610209;178610208	chr2:179474937;179474936;179474935
Novex-1	8166	24721;24722;24723	chr2:178610210;178610209;178610208	chr2:179474937;179474936;179474935
Novex-2	8233	24922;24923;24924	chr2:178610210;178610209;178610208	chr2:179474937;179474936;179474935
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Fn3-12
• Domain position: 60
• Structural Position: 91
• Q(SASA): 0.269
• 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
W/R	rs1360832418	-1.808	1.0	N	0.886	0.554	0.51748813702	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.64E-05	0	0
W/R	rs1360832418	-1.808	1.0	N	0.886	0.554	0.51748813702	gnomAD-4.0.0	3.42242E-06	None	None	None	None	N	None	0	0	None	0	0	None	5.61798E-05	0	0	2.31927E-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
W/A	0.7272	likely_pathogenic	0.7861	pathogenic	-2.879	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
W/C	0.7254	likely_pathogenic	0.7774	pathogenic	-1.911	Destabilizing	1.0	D	0.847	deleterious	N	0.421413615	None	None	N
W/D	0.9754	likely_pathogenic	0.9821	pathogenic	-2.398	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
W/E	0.9615	likely_pathogenic	0.9718	pathogenic	-2.295	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
W/F	0.1786	likely_benign	0.1999	benign	-1.803	Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	N
W/G	0.7007	likely_pathogenic	0.7548	pathogenic	-3.107	Highly Destabilizing	1.0	D	0.723	prob.delet.	N	0.505434934	None	None	N
W/H	0.7741	likely_pathogenic	0.7438	pathogenic	-1.769	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
W/I	0.7512	likely_pathogenic	0.8229	pathogenic	-2.035	Highly Destabilizing	1.0	D	0.871	deleterious	None	None	None	None	N
W/K	0.9635	likely_pathogenic	0.9701	pathogenic	-2.383	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
W/L	0.6423	likely_pathogenic	0.7221	pathogenic	-2.035	Highly Destabilizing	1.0	D	0.723	prob.delet.	N	0.437823075	None	None	N
W/M	0.7375	likely_pathogenic	0.8064	pathogenic	-1.65	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	N
W/N	0.9329	likely_pathogenic	0.9457	pathogenic	-2.979	Highly Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
W/P	0.9974	likely_pathogenic	0.997	pathogenic	-2.339	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
W/Q	0.9282	likely_pathogenic	0.9378	pathogenic	-2.809	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
W/R	0.9346	likely_pathogenic	0.9407	pathogenic	-2.087	Highly Destabilizing	1.0	D	0.886	deleterious	N	0.464505476	None	None	N
W/S	0.6741	likely_pathogenic	0.7361	pathogenic	-3.269	Highly Destabilizing	1.0	D	0.847	deleterious	N	0.486849173	None	None	N
W/T	0.7903	likely_pathogenic	0.8453	pathogenic	-3.107	Highly Destabilizing	1.0	D	0.803	deleterious	None	None	None	None	N
W/V	0.6393	likely_pathogenic	0.7207	pathogenic	-2.339	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
W/Y	0.4011	ambiguous	0.4163	ambiguous	-1.715	Destabilizing	1.0	D	0.673	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.