TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35769	107530;107531;107532	chr2:178528346;178528345;178528344	chr2:179393073;179393072;179393071
N2AB	34128	102607;102608;102609	chr2:178528346;178528345;178528344	chr2:179393073;179393072;179393071
N2A	33201	99826;99827;99828	chr2:178528346;178528345;178528344	chr2:179393073;179393072;179393071
N2B	26704	80335;80336;80337	chr2:178528346;178528345;178528344	chr2:179393073;179393072;179393071
Novex-1	26829	80710;80711;80712	chr2:178528346;178528345;178528344	chr2:179393073;179393072;179393071
Novex-2	26896	80911;80912;80913	chr2:178528346;178528345;178528344	chr2:179393073;179393072;179393071
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-168
• Domain position: 68
• Structural Position: 151
• Q(SASA): 0.2716
• 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
S/R	None	None	0.934	N	0.481	0.437	0.346992582518	gnomAD-4.0.0	4.10499E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	4.49711E-06	0	1.6564E-05

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
S/A	0.1151	likely_benign	0.1056	benign	-0.833	Destabilizing	0.525	D	0.441	neutral	None	None	None	None	I
S/C	0.2804	likely_benign	0.2832	benign	-0.532	Destabilizing	0.997	D	0.478	neutral	N	0.492902167	None	None	I
S/D	0.8382	likely_pathogenic	0.8135	pathogenic	0.112	Stabilizing	0.842	D	0.381	neutral	None	None	None	None	I
S/E	0.8667	likely_pathogenic	0.7984	pathogenic	0.069	Stabilizing	0.842	D	0.394	neutral	None	None	None	None	I
S/F	0.6509	likely_pathogenic	0.5931	pathogenic	-1.241	Destabilizing	0.949	D	0.578	neutral	None	None	None	None	I
S/G	0.1609	likely_benign	0.151	benign	-1.01	Destabilizing	0.801	D	0.404	neutral	N	0.509588039	None	None	I
S/H	0.7774	likely_pathogenic	0.7517	pathogenic	-1.484	Destabilizing	0.037	N	0.399	neutral	None	None	None	None	I
S/I	0.5076	ambiguous	0.4491	ambiguous	-0.477	Destabilizing	0.028	N	0.391	neutral	N	0.496509792	None	None	I
S/K	0.9304	likely_pathogenic	0.9072	pathogenic	-0.548	Destabilizing	0.842	D	0.386	neutral	None	None	None	None	I
S/L	0.3091	likely_benign	0.2706	benign	-0.477	Destabilizing	0.728	D	0.496	neutral	None	None	None	None	I
S/M	0.4803	ambiguous	0.4453	ambiguous	-0.091	Destabilizing	0.949	D	0.495	neutral	None	None	None	None	I
S/N	0.39	ambiguous	0.3665	ambiguous	-0.397	Destabilizing	0.801	D	0.43	neutral	D	0.534465053	None	None	I
S/P	0.9011	likely_pathogenic	0.8704	pathogenic	-0.566	Destabilizing	0.974	D	0.489	neutral	None	None	None	None	I
S/Q	0.8185	likely_pathogenic	0.775	pathogenic	-0.644	Destabilizing	0.974	D	0.418	neutral	None	None	None	None	I
S/R	0.865	likely_pathogenic	0.8193	pathogenic	-0.394	Destabilizing	0.934	D	0.481	neutral	N	0.495946738	None	None	I
S/T	0.1512	likely_benign	0.1603	benign	-0.548	Destabilizing	0.051	N	0.301	neutral	N	0.497754892	None	None	I
S/V	0.5203	ambiguous	0.482	ambiguous	-0.566	Destabilizing	0.728	D	0.489	neutral	None	None	None	None	I
S/W	0.8432	likely_pathogenic	0.7789	pathogenic	-1.14	Destabilizing	0.998	D	0.683	prob.neutral	None	None	None	None	I
S/Y	0.6148	likely_pathogenic	0.5416	ambiguous	-0.896	Destabilizing	0.949	D	0.579	neutral	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.