TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17842	53749;53750;53751	chr2:178607078;178607077;178607076	chr2:179471805;179471804;179471803
N2AB	16201	48826;48827;48828	chr2:178607078;178607077;178607076	chr2:179471805;179471804;179471803
N2A	15274	46045;46046;46047	chr2:178607078;178607077;178607076	chr2:179471805;179471804;179471803
N2B	8777	26554;26555;26556	chr2:178607078;178607077;178607076	chr2:179471805;179471804;179471803
Novex-1	8902	26929;26930;26931	chr2:178607078;178607077;178607076	chr2:179471805;179471804;179471803
Novex-2	8969	27130;27131;27132	chr2:178607078;178607077;178607076	chr2:179471805;179471804;179471803
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-17
• Domain position: 79
• Structural Position: 113
• Q(SASA): 0.442
• 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
K/N	None	None	1.0	N	0.675	0.377	0.276482976112	gnomAD-4.0.0	6.84901E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	9.00003E-07	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
K/A	0.7633	likely_pathogenic	0.6303	pathogenic	-0.115	Destabilizing	0.999	D	0.604	neutral	None	None	None	None	I
K/C	0.9018	likely_pathogenic	0.862	pathogenic	-0.474	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
K/D	0.8789	likely_pathogenic	0.8154	pathogenic	-0.019	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	I
K/E	0.579	likely_pathogenic	0.4201	ambiguous	-0.006	Destabilizing	0.999	D	0.567	neutral	N	0.465204464	None	None	I
K/F	0.9729	likely_pathogenic	0.9477	pathogenic	-0.388	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	I
K/G	0.9061	likely_pathogenic	0.8261	pathogenic	-0.288	Destabilizing	1.0	D	0.575	neutral	None	None	None	None	I
K/H	0.5863	likely_pathogenic	0.5247	ambiguous	-0.447	Destabilizing	1.0	D	0.578	neutral	None	None	None	None	I
K/I	0.6516	likely_pathogenic	0.524	ambiguous	0.26	Stabilizing	1.0	D	0.628	neutral	None	None	None	None	I
K/L	0.7522	likely_pathogenic	0.6323	pathogenic	0.26	Stabilizing	1.0	D	0.575	neutral	None	None	None	None	I
K/M	0.6299	likely_pathogenic	0.4944	ambiguous	-0.058	Destabilizing	1.0	D	0.577	neutral	D	0.522964689	None	None	I
K/N	0.7989	likely_pathogenic	0.6919	pathogenic	-0.036	Destabilizing	1.0	D	0.675	prob.neutral	N	0.480078517	None	None	I
K/P	0.8948	likely_pathogenic	0.7935	pathogenic	0.161	Stabilizing	1.0	D	0.617	neutral	None	None	None	None	I
K/Q	0.3256	likely_benign	0.2527	benign	-0.146	Destabilizing	1.0	D	0.671	neutral	N	0.516998722	None	None	I
K/R	0.0998	likely_benign	0.0938	benign	-0.098	Destabilizing	0.999	D	0.492	neutral	N	0.49131363	None	None	I
K/S	0.8395	likely_pathogenic	0.7277	pathogenic	-0.491	Destabilizing	0.999	D	0.615	neutral	None	None	None	None	I
K/T	0.5161	ambiguous	0.3536	ambiguous	-0.331	Destabilizing	1.0	D	0.621	neutral	N	0.467961743	None	None	I
K/V	0.6434	likely_pathogenic	0.5203	ambiguous	0.161	Stabilizing	1.0	D	0.619	neutral	None	None	None	None	I
K/W	0.9599	likely_pathogenic	0.935	pathogenic	-0.442	Destabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	I
K/Y	0.8995	likely_pathogenic	0.8494	pathogenic	-0.086	Destabilizing	1.0	D	0.621	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.