TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23168	69727;69728;69729	chr2:178576742;178576741;178576740	chr2:179441469;179441468;179441467
N2AB	21527	64804;64805;64806	chr2:178576742;178576741;178576740	chr2:179441469;179441468;179441467
N2A	20600	62023;62024;62025	chr2:178576742;178576741;178576740	chr2:179441469;179441468;179441467
N2B	14103	42532;42533;42534	chr2:178576742;178576741;178576740	chr2:179441469;179441468;179441467
Novex-1	14228	42907;42908;42909	chr2:178576742;178576741;178576740	chr2:179441469;179441468;179441467
Novex-2	14295	43108;43109;43110	chr2:178576742;178576741;178576740	chr2:179441469;179441468;179441467
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGC
• RefSeq wild type template codon: CCG
• Domain: Fn3-56
• Domain position: 30
• Structural Position: 32
• Q(SASA): 0.7597
• 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
G/D	None	None	1.0	N	0.691	0.495	0.439551795455	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
G/A	0.7049	likely_pathogenic	0.6826	pathogenic	-0.191	Destabilizing	1.0	D	0.615	neutral	N	0.495948409	None	None	I
G/C	0.7214	likely_pathogenic	0.693	pathogenic	-0.88	Destabilizing	1.0	D	0.791	deleterious	D	0.53147581	None	None	I
G/D	0.8418	likely_pathogenic	0.83	pathogenic	-0.427	Destabilizing	1.0	D	0.691	prob.neutral	N	0.515320111	None	None	I
G/E	0.8734	likely_pathogenic	0.8687	pathogenic	-0.575	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
G/F	0.9456	likely_pathogenic	0.9385	pathogenic	-0.953	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
G/H	0.8739	likely_pathogenic	0.8409	pathogenic	-0.29	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	I
G/I	0.9451	likely_pathogenic	0.9453	pathogenic	-0.459	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
G/K	0.8733	likely_pathogenic	0.8365	pathogenic	-0.427	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
G/L	0.9262	likely_pathogenic	0.9119	pathogenic	-0.459	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
G/M	0.9387	likely_pathogenic	0.9319	pathogenic	-0.528	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	I
G/N	0.7885	likely_pathogenic	0.7586	pathogenic	-0.209	Destabilizing	1.0	D	0.674	neutral	None	None	None	None	I
G/P	0.9949	likely_pathogenic	0.995	pathogenic	-0.347	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
G/Q	0.8158	likely_pathogenic	0.786	pathogenic	-0.452	Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	I
G/R	0.7809	likely_pathogenic	0.7406	pathogenic	-0.084	Destabilizing	1.0	D	0.79	deleterious	N	0.512611086	None	None	I
G/S	0.4869	ambiguous	0.4689	ambiguous	-0.357	Destabilizing	1.0	D	0.694	prob.neutral	N	0.50142891	None	None	I
G/T	0.8594	likely_pathogenic	0.8478	pathogenic	-0.441	Destabilizing	1.0	D	0.79	deleterious	None	None	None	None	I
G/V	0.9154	likely_pathogenic	0.9132	pathogenic	-0.347	Destabilizing	1.0	D	0.797	deleterious	D	0.530461852	None	None	I
G/W	0.9218	likely_pathogenic	0.9165	pathogenic	-1.046	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	I
G/Y	0.9049	likely_pathogenic	0.8975	pathogenic	-0.734	Destabilizing	1.0	D	0.773	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.