TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19515	58768;58769;58770	chr2:178593757;178593756;178593755	chr2:179458484;179458483;179458482
N2AB	17874	53845;53846;53847	chr2:178593757;178593756;178593755	chr2:179458484;179458483;179458482
N2A	16947	51064;51065;51066	chr2:178593757;178593756;178593755	chr2:179458484;179458483;179458482
N2B	10450	31573;31574;31575	chr2:178593757;178593756;178593755	chr2:179458484;179458483;179458482
Novex-1	10575	31948;31949;31950	chr2:178593757;178593756;178593755	chr2:179458484;179458483;179458482
Novex-2	10642	32149;32150;32151	chr2:178593757;178593756;178593755	chr2:179458484;179458483;179458482
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: Fn3-29
• Domain position: 37
• Structural Position: 38
• Q(SASA): 0.1287
• 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
Y/C	rs1353143854	-2.003	1.0	D	0.858	0.919	0.87881004843	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
Y/C	rs1353143854	-2.003	1.0	D	0.858	0.919	0.87881004843	gnomAD-4.0.0	6.84406E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99577E-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	0.9977	likely_pathogenic	0.9967	pathogenic	-3.598	Highly Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
Y/C	0.9406	likely_pathogenic	0.9212	pathogenic	-2.27	Highly Destabilizing	1.0	D	0.858	deleterious	D	0.632850028	None	None	N
Y/D	0.9958	likely_pathogenic	0.9938	pathogenic	-3.891	Highly Destabilizing	1.0	D	0.892	deleterious	D	0.649303358	None	None	N
Y/E	0.9992	likely_pathogenic	0.9988	pathogenic	-3.686	Highly Destabilizing	1.0	D	0.89	deleterious	None	None	None	None	N
Y/F	0.2773	likely_benign	0.3202	benign	-1.289	Destabilizing	0.999	D	0.674	neutral	D	0.560002125	None	None	N
Y/G	0.9911	likely_pathogenic	0.9886	pathogenic	-3.998	Highly Destabilizing	1.0	D	0.906	deleterious	None	None	None	None	N
Y/H	0.978	likely_pathogenic	0.9744	pathogenic	-2.577	Highly Destabilizing	1.0	D	0.822	deleterious	D	0.648697945	None	None	N
Y/I	0.9781	likely_pathogenic	0.973	pathogenic	-2.242	Highly Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
Y/K	0.9989	likely_pathogenic	0.9985	pathogenic	-2.467	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
Y/L	0.9562	likely_pathogenic	0.949	pathogenic	-2.242	Highly Destabilizing	0.999	D	0.745	deleterious	None	None	None	None	N
Y/M	0.9885	likely_pathogenic	0.9862	pathogenic	-2.126	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/N	0.9789	likely_pathogenic	0.9707	pathogenic	-3.208	Highly Destabilizing	1.0	D	0.878	deleterious	D	0.649101554	None	None	N
Y/P	0.9995	likely_pathogenic	0.9993	pathogenic	-2.713	Highly Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
Y/Q	0.9988	likely_pathogenic	0.9983	pathogenic	-2.98	Highly Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/R	0.9953	likely_pathogenic	0.9938	pathogenic	-2.149	Highly Destabilizing	1.0	D	0.881	deleterious	None	None	None	None	N
Y/S	0.9903	likely_pathogenic	0.9865	pathogenic	-3.551	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.649101554	None	None	N
Y/T	0.9958	likely_pathogenic	0.9943	pathogenic	-3.227	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
Y/V	0.9649	likely_pathogenic	0.9545	pathogenic	-2.713	Highly Destabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
Y/W	0.898	likely_pathogenic	0.8958	pathogenic	-0.505	Destabilizing	1.0	D	0.807	deleterious	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.