TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24334	73225;73226;73227	chr2:178573132;178573131;178573130	chr2:179437859;179437858;179437857
N2AB	22693	68302;68303;68304	chr2:178573132;178573131;178573130	chr2:179437859;179437858;179437857
N2A	21766	65521;65522;65523	chr2:178573132;178573131;178573130	chr2:179437859;179437858;179437857
N2B	15269	46030;46031;46032	chr2:178573132;178573131;178573130	chr2:179437859;179437858;179437857
Novex-1	15394	46405;46406;46407	chr2:178573132;178573131;178573130	chr2:179437859;179437858;179437857
Novex-2	15461	46606;46607;46608	chr2:178573132;178573131;178573130	chr2:179437859;179437858;179437857
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-65
• Domain position: 12
• Structural Position: 14
• Q(SASA): 0.5785
• 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
D/Y	None	None	0.999	N	0.691	0.456	0.601252736945	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.625E-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
D/A	0.937	likely_pathogenic	0.9422	pathogenic	-0.468	Destabilizing	0.988	D	0.635	neutral	N	0.466747202	None	None	N
D/C	0.9922	likely_pathogenic	0.9934	pathogenic	0.085	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	N
D/E	0.8255	likely_pathogenic	0.8571	pathogenic	-0.301	Destabilizing	0.958	D	0.4	neutral	N	0.487137174	None	None	N
D/F	0.9884	likely_pathogenic	0.989	pathogenic	-0.438	Destabilizing	1.0	D	0.696	prob.neutral	None	None	None	None	N
D/G	0.8936	likely_pathogenic	0.8944	pathogenic	-0.666	Destabilizing	0.919	D	0.635	neutral	N	0.479446634	None	None	N
D/H	0.9624	likely_pathogenic	0.9628	pathogenic	-0.44	Destabilizing	0.998	D	0.685	prob.neutral	N	0.493653776	None	None	N
D/I	0.9913	likely_pathogenic	0.9921	pathogenic	0.011	Stabilizing	0.995	D	0.74	deleterious	None	None	None	None	N
D/K	0.9886	likely_pathogenic	0.9892	pathogenic	0.329	Stabilizing	0.991	D	0.697	prob.neutral	None	None	None	None	N
D/L	0.9755	likely_pathogenic	0.9783	pathogenic	0.011	Stabilizing	0.995	D	0.721	prob.delet.	None	None	None	None	N
D/M	0.9949	likely_pathogenic	0.9951	pathogenic	0.308	Stabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
D/N	0.7017	likely_pathogenic	0.7155	pathogenic	0.016	Stabilizing	0.142	N	0.285	neutral	N	0.465088134	None	None	N
D/P	0.9989	likely_pathogenic	0.9985	pathogenic	-0.127	Destabilizing	0.998	D	0.739	prob.delet.	None	None	None	None	N
D/Q	0.9731	likely_pathogenic	0.9753	pathogenic	0.038	Stabilizing	0.991	D	0.698	prob.neutral	None	None	None	None	N
D/R	0.984	likely_pathogenic	0.9846	pathogenic	0.381	Stabilizing	0.991	D	0.685	prob.neutral	None	None	None	None	N
D/S	0.8388	likely_pathogenic	0.85	pathogenic	-0.093	Destabilizing	0.938	D	0.591	neutral	None	None	None	None	N
D/T	0.9605	likely_pathogenic	0.9627	pathogenic	0.067	Stabilizing	0.991	D	0.703	prob.neutral	None	None	None	None	N
D/V	0.9701	likely_pathogenic	0.9733	pathogenic	-0.127	Destabilizing	0.994	D	0.721	prob.delet.	N	0.488436309	None	None	N
D/W	0.9979	likely_pathogenic	0.9977	pathogenic	-0.28	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	N
D/Y	0.926	likely_pathogenic	0.9348	pathogenic	-0.194	Destabilizing	0.999	D	0.691	prob.neutral	N	0.495135033	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.