TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21702	65329;65330;65331	chr2:178584447;178584446;178584445	chr2:179449174;179449173;179449172
N2AB	20061	60406;60407;60408	chr2:178584447;178584446;178584445	chr2:179449174;179449173;179449172
N2A	19134	57625;57626;57627	chr2:178584447;178584446;178584445	chr2:179449174;179449173;179449172
N2B	12637	38134;38135;38136	chr2:178584447;178584446;178584445	chr2:179449174;179449173;179449172
Novex-1	12762	38509;38510;38511	chr2:178584447;178584446;178584445	chr2:179449174;179449173;179449172
Novex-2	12829	38710;38711;38712	chr2:178584447;178584446;178584445	chr2:179449174;179449173;179449172
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Fn3-45
• Domain position: 44
• Structural Position: 54
• Q(SASA): 0.8294
• 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
N/K	rs753302897	0.496	1.0	N	0.553	0.348	0.218845423259	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
N/K	rs753302897	0.496	1.0	N	0.553	0.348	0.218845423259	gnomAD-4.0.0	1.5923E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43303E-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
N/A	0.8667	likely_pathogenic	0.8123	pathogenic	-0.104	Destabilizing	1.0	D	0.563	neutral	None	None	None	None	I
N/C	0.8182	likely_pathogenic	0.7718	pathogenic	0.17	Stabilizing	1.0	D	0.714	prob.delet.	None	None	None	None	I
N/D	0.7379	likely_pathogenic	0.6639	pathogenic	0.099	Stabilizing	0.999	D	0.565	neutral	N	0.490948271	None	None	I
N/E	0.9455	likely_pathogenic	0.9199	pathogenic	0.04	Stabilizing	0.999	D	0.547	neutral	None	None	None	None	I
N/F	0.9551	likely_pathogenic	0.9404	pathogenic	-0.68	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
N/G	0.7509	likely_pathogenic	0.6771	pathogenic	-0.207	Destabilizing	0.999	D	0.487	neutral	None	None	None	None	I
N/H	0.5132	ambiguous	0.4391	ambiguous	-0.191	Destabilizing	1.0	D	0.581	neutral	N	0.478146869	None	None	I
N/I	0.9021	likely_pathogenic	0.8779	pathogenic	0.067	Stabilizing	1.0	D	0.693	prob.neutral	N	0.486135812	None	None	I
N/K	0.9269	likely_pathogenic	0.893	pathogenic	0.147	Stabilizing	1.0	D	0.553	neutral	N	0.507131232	None	None	I
N/L	0.8155	likely_pathogenic	0.7767	pathogenic	0.067	Stabilizing	1.0	D	0.676	prob.neutral	None	None	None	None	I
N/M	0.8809	likely_pathogenic	0.8545	pathogenic	0.15	Stabilizing	1.0	D	0.632	neutral	None	None	None	None	I
N/P	0.9457	likely_pathogenic	0.9288	pathogenic	0.034	Stabilizing	1.0	D	0.641	neutral	None	None	None	None	I
N/Q	0.8873	likely_pathogenic	0.8464	pathogenic	-0.278	Destabilizing	1.0	D	0.573	neutral	None	None	None	None	I
N/R	0.9081	likely_pathogenic	0.8686	pathogenic	0.238	Stabilizing	1.0	D	0.586	neutral	None	None	None	None	I
N/S	0.3394	likely_benign	0.2894	benign	-0.047	Destabilizing	0.999	D	0.499	neutral	N	0.499607826	None	None	I
N/T	0.6579	likely_pathogenic	0.6022	pathogenic	0.013	Stabilizing	0.999	D	0.541	neutral	N	0.497703672	None	None	I
N/V	0.8984	likely_pathogenic	0.8674	pathogenic	0.034	Stabilizing	1.0	D	0.679	prob.neutral	None	None	None	None	I
N/W	0.98	likely_pathogenic	0.9719	pathogenic	-0.793	Destabilizing	1.0	D	0.715	prob.delet.	None	None	None	None	I
N/Y	0.6636	likely_pathogenic	0.6089	pathogenic	-0.469	Destabilizing	1.0	D	0.634	neutral	N	0.473133666	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.