TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20306	61141;61142;61143	chr2:178590809;178590808;178590807	chr2:179455536;179455535;179455534
N2AB	18665	56218;56219;56220	chr2:178590809;178590808;178590807	chr2:179455536;179455535;179455534
N2A	17738	53437;53438;53439	chr2:178590809;178590808;178590807	chr2:179455536;179455535;179455534
N2B	11241	33946;33947;33948	chr2:178590809;178590808;178590807	chr2:179455536;179455535;179455534
Novex-1	11366	34321;34322;34323	chr2:178590809;178590808;178590807	chr2:179455536;179455535;179455534
Novex-2	11433	34522;34523;34524	chr2:178590809;178590808;178590807	chr2:179455536;179455535;179455534
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Fn3-35
• Domain position: 36
• Structural Position: 38
• Q(SASA): 0.104
• 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/H	None	None	1.0	D	0.819	0.832	0.807651778373	gnomAD-4.0.0	1.37445E-06	None	None	None	None	N	None	0	0	None	0	2.53627E-05	None	0	0	0	0	1.66478E-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
Y/A	0.9945	likely_pathogenic	0.9946	pathogenic	-3.063	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
Y/C	0.8186	likely_pathogenic	0.8437	pathogenic	-1.751	Destabilizing	1.0	D	0.873	deleterious	D	0.663263597	None	None	N
Y/D	0.996	likely_pathogenic	0.9959	pathogenic	-3.728	Highly Destabilizing	1.0	D	0.92	deleterious	D	0.663465402	None	None	N
Y/E	0.9989	likely_pathogenic	0.9988	pathogenic	-3.501	Highly Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
Y/F	0.1941	likely_benign	0.2053	benign	-1.215	Destabilizing	0.999	D	0.653	neutral	D	0.563948924	None	None	N
Y/G	0.9839	likely_pathogenic	0.9844	pathogenic	-3.488	Highly Destabilizing	1.0	D	0.932	deleterious	None	None	None	None	N
Y/H	0.9659	likely_pathogenic	0.9642	pathogenic	-2.338	Highly Destabilizing	1.0	D	0.819	deleterious	D	0.646840628	None	None	N
Y/I	0.9545	likely_pathogenic	0.9551	pathogenic	-1.634	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
Y/K	0.9979	likely_pathogenic	0.9977	pathogenic	-2.467	Highly Destabilizing	1.0	D	0.908	deleterious	None	None	None	None	N
Y/L	0.9238	likely_pathogenic	0.922	pathogenic	-1.634	Destabilizing	0.999	D	0.761	deleterious	None	None	None	None	N
Y/M	0.9753	likely_pathogenic	0.9773	pathogenic	-1.335	Destabilizing	1.0	D	0.847	deleterious	None	None	None	None	N
Y/N	0.9638	likely_pathogenic	0.9613	pathogenic	-3.388	Highly Destabilizing	1.0	D	0.902	deleterious	D	0.663263597	None	None	N
Y/P	0.999	likely_pathogenic	0.9989	pathogenic	-2.128	Highly Destabilizing	1.0	D	0.945	deleterious	None	None	None	None	N
Y/Q	0.9973	likely_pathogenic	0.9971	pathogenic	-3.055	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
Y/R	0.9922	likely_pathogenic	0.9912	pathogenic	-2.379	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
Y/S	0.9807	likely_pathogenic	0.9806	pathogenic	-3.64	Highly Destabilizing	1.0	D	0.912	deleterious	D	0.663263597	None	None	N
Y/T	0.9929	likely_pathogenic	0.9927	pathogenic	-3.286	Highly Destabilizing	1.0	D	0.912	deleterious	None	None	None	None	N
Y/V	0.9406	likely_pathogenic	0.9412	pathogenic	-2.128	Highly Destabilizing	1.0	D	0.789	deleterious	None	None	None	None	N
Y/W	0.8361	likely_pathogenic	0.8352	pathogenic	-0.553	Destabilizing	1.0	D	0.801	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.