TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27596	83011;83012;83013	chr2:178563346;178563345;178563344	chr2:179428073;179428072;179428071
N2AB	25955	78088;78089;78090	chr2:178563346;178563345;178563344	chr2:179428073;179428072;179428071
N2A	25028	75307;75308;75309	chr2:178563346;178563345;178563344	chr2:179428073;179428072;179428071
N2B	18531	55816;55817;55818	chr2:178563346;178563345;178563344	chr2:179428073;179428072;179428071
Novex-1	18656	56191;56192;56193	chr2:178563346;178563345;178563344	chr2:179428073;179428072;179428071
Novex-2	18723	56392;56393;56394	chr2:178563346;178563345;178563344	chr2:179428073;179428072;179428071
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-89
• Domain position: 27
• Structural Position: 29
• Q(SASA): 0.4443
• 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
Y/C	None	None	0.999	N	0.615	0.343	0.432604763906	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
Y/A	0.8913	likely_pathogenic	0.8975	pathogenic	-0.87	Destabilizing	0.845	D	0.501	neutral	None	None	None	None	I
Y/C	0.563	ambiguous	0.5667	pathogenic	0.024	Stabilizing	0.999	D	0.615	neutral	N	0.482365787	None	None	I
Y/D	0.7838	likely_pathogenic	0.7952	pathogenic	0.911	Stabilizing	0.967	D	0.664	neutral	N	0.463833453	None	None	I
Y/E	0.9536	likely_pathogenic	0.9574	pathogenic	0.895	Stabilizing	0.975	D	0.5	neutral	None	None	None	None	I
Y/F	0.2577	likely_benign	0.249	benign	-0.457	Destabilizing	0.944	D	0.473	neutral	N	0.506701583	None	None	I
Y/G	0.8253	likely_pathogenic	0.8387	pathogenic	-1.063	Destabilizing	0.845	D	0.555	neutral	None	None	None	None	I
Y/H	0.6692	likely_pathogenic	0.6648	pathogenic	0.103	Stabilizing	0.994	D	0.553	neutral	N	0.463652421	None	None	I
Y/I	0.9067	likely_pathogenic	0.898	pathogenic	-0.381	Destabilizing	0.987	D	0.584	neutral	None	None	None	None	I
Y/K	0.9417	likely_pathogenic	0.941	pathogenic	0.096	Stabilizing	0.975	D	0.518	neutral	None	None	None	None	I
Y/L	0.8287	likely_pathogenic	0.818	pathogenic	-0.381	Destabilizing	0.916	D	0.573	neutral	None	None	None	None	I
Y/M	0.9117	likely_pathogenic	0.9101	pathogenic	-0.14	Destabilizing	0.999	D	0.552	neutral	None	None	None	None	I
Y/N	0.6304	likely_pathogenic	0.6539	pathogenic	-0.079	Destabilizing	0.967	D	0.613	neutral	N	0.479706983	None	None	I
Y/P	0.9839	likely_pathogenic	0.9848	pathogenic	-0.524	Destabilizing	0.987	D	0.675	neutral	None	None	None	None	I
Y/Q	0.9159	likely_pathogenic	0.9217	pathogenic	-0.056	Destabilizing	0.975	D	0.579	neutral	None	None	None	None	I
Y/R	0.8437	likely_pathogenic	0.8456	pathogenic	0.417	Stabilizing	0.975	D	0.619	neutral	None	None	None	None	I
Y/S	0.5841	likely_pathogenic	0.6101	pathogenic	-0.561	Destabilizing	0.204	N	0.404	neutral	N	0.468855271	None	None	I
Y/T	0.8417	likely_pathogenic	0.8549	pathogenic	-0.488	Destabilizing	0.95	D	0.479	neutral	None	None	None	None	I
Y/V	0.8372	likely_pathogenic	0.8278	pathogenic	-0.524	Destabilizing	0.975	D	0.54	neutral	None	None	None	None	I
Y/W	0.6745	likely_pathogenic	0.6547	pathogenic	-0.522	Destabilizing	0.999	D	0.526	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.