TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32556	97891;97892;97893	chr2:178541411;178541410;178541409	chr2:179406138;179406137;179406136
N2AB	30915	92968;92969;92970	chr2:178541411;178541410;178541409	chr2:179406138;179406137;179406136
N2A	29988	90187;90188;90189	chr2:178541411;178541410;178541409	chr2:179406138;179406137;179406136
N2B	23491	70696;70697;70698	chr2:178541411;178541410;178541409	chr2:179406138;179406137;179406136
Novex-1	23616	71071;71072;71073	chr2:178541411;178541410;178541409	chr2:179406138;179406137;179406136
Novex-2	23683	71272;71273;71274	chr2:178541411;178541410;178541409	chr2:179406138;179406137;179406136
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: M
• RefSeq wild type transcript codon: ATG
• RefSeq wild type template codon: TAC
• Domain: Fn3-125
• Domain position: 58
• Structural Position: 88
• Q(SASA): 0.3256
• 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
M/I	None	None	0.985	N	0.487	0.321	0.683392867763	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-06	0	0
M/T	rs1257976666	-0.863	0.994	N	0.526	0.49	0.7584815763	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.29E-05	None	0	0	0
M/T	rs1257976666	-0.863	0.994	N	0.526	0.49	0.7584815763	gnomAD-4.0.0	1.59281E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.4362E-05	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
M/A	0.3952	ambiguous	0.359	ambiguous	-0.692	Destabilizing	0.989	D	0.509	neutral	None	None	None	None	I
M/C	0.8177	likely_pathogenic	0.7838	pathogenic	-0.803	Destabilizing	1.0	D	0.593	neutral	None	None	None	None	I
M/D	0.843	likely_pathogenic	0.8076	pathogenic	0.117	Stabilizing	0.999	D	0.644	neutral	None	None	None	None	I
M/E	0.5838	likely_pathogenic	0.5414	ambiguous	0.127	Stabilizing	0.999	D	0.527	neutral	None	None	None	None	I
M/F	0.5576	ambiguous	0.5244	ambiguous	-0.063	Destabilizing	0.999	D	0.462	neutral	None	None	None	None	I
M/G	0.5975	likely_pathogenic	0.5702	pathogenic	-0.919	Destabilizing	0.995	D	0.54	neutral	None	None	None	None	I
M/H	0.6986	likely_pathogenic	0.6682	pathogenic	0.075	Stabilizing	1.0	D	0.645	neutral	None	None	None	None	I
M/I	0.7223	likely_pathogenic	0.6609	pathogenic	-0.154	Destabilizing	0.985	D	0.487	neutral	N	0.460894723	None	None	I
M/K	0.4038	ambiguous	0.3565	ambiguous	0.097	Stabilizing	0.994	D	0.527	neutral	N	0.41100462	None	None	I
M/L	0.2269	likely_benign	0.2011	benign	-0.154	Destabilizing	0.927	D	0.255	neutral	N	0.451467163	None	None	I
M/N	0.6039	likely_pathogenic	0.5599	ambiguous	0.04	Stabilizing	0.999	D	0.637	neutral	None	None	None	None	I
M/P	0.9543	likely_pathogenic	0.9352	pathogenic	-0.306	Destabilizing	0.999	D	0.638	neutral	None	None	None	None	I
M/Q	0.3086	likely_benign	0.2942	benign	-0.013	Destabilizing	0.999	D	0.469	neutral	None	None	None	None	I
M/R	0.4206	ambiguous	0.3907	ambiguous	0.549	Stabilizing	0.998	D	0.529	neutral	N	0.435246917	None	None	I
M/S	0.4253	ambiguous	0.4022	ambiguous	-0.444	Destabilizing	0.995	D	0.493	neutral	None	None	None	None	I
M/T	0.3555	ambiguous	0.3104	benign	-0.324	Destabilizing	0.994	D	0.526	neutral	N	0.407673526	None	None	I
M/V	0.1622	likely_benign	0.1427	benign	-0.306	Destabilizing	0.985	D	0.407	neutral	N	0.429918455	None	None	I
M/W	0.8709	likely_pathogenic	0.8464	pathogenic	-0.077	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	I
M/Y	0.7565	likely_pathogenic	0.7297	pathogenic	0.038	Stabilizing	0.999	D	0.593	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.