TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21692	65299;65300;65301	chr2:178584477;178584476;178584475	chr2:179449204;179449203;179449202
N2AB	20051	60376;60377;60378	chr2:178584477;178584476;178584475	chr2:179449204;179449203;179449202
N2A	19124	57595;57596;57597	chr2:178584477;178584476;178584475	chr2:179449204;179449203;179449202
N2B	12627	38104;38105;38106	chr2:178584477;178584476;178584475	chr2:179449204;179449203;179449202
Novex-1	12752	38479;38480;38481	chr2:178584477;178584476;178584475	chr2:179449204;179449203;179449202
Novex-2	12819	38680;38681;38682	chr2:178584477;178584476;178584475	chr2:179449204;179449203;179449202
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-45
• Domain position: 34
• Structural Position: 36
• Q(SASA): 0.4751
• 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
I/V	rs758476009	-0.591	0.001	N	0.13	0.129	0.402043589563	gnomAD-2.1.1	1.03674E-04	None	None	None	None	I	None	0	0	None	0	0	None	0	None	7.99744E-04	7.04E-05	0
I/V	rs758476009	-0.591	0.001	N	0.13	0.129	0.402043589563	gnomAD-3.1.2	5.26E-05	None	None	None	None	I	None	0	0	0	0	0	None	4.7081E-04	0	4.41E-05	0	0
I/V	rs758476009	-0.591	0.001	N	0.13	0.129	0.402043589563	gnomAD-4.0.0	1.06004E-04	None	None	None	None	I	None	0	0	None	0	0	None	7.81079E-04	0	9.83439E-05	0	8.00948E-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
I/A	0.1074	likely_benign	0.1068	benign	-1.227	Destabilizing	0.002	N	0.24	neutral	None	None	None	None	I
I/C	0.5086	ambiguous	0.4451	ambiguous	-0.748	Destabilizing	0.245	N	0.271	neutral	None	None	None	None	I
I/D	0.4981	ambiguous	0.4273	ambiguous	-0.42	Destabilizing	0.018	N	0.336	neutral	None	None	None	None	I
I/E	0.3628	ambiguous	0.3067	benign	-0.446	Destabilizing	0.018	N	0.33	neutral	None	None	None	None	I
I/F	0.1572	likely_benign	0.1423	benign	-0.847	Destabilizing	0.065	N	0.219	neutral	N	0.467659028	None	None	I
I/G	0.3703	ambiguous	0.3412	ambiguous	-1.504	Destabilizing	0.008	N	0.306	neutral	None	None	None	None	I
I/H	0.3388	likely_benign	0.2958	benign	-0.639	Destabilizing	0.497	N	0.333	neutral	None	None	None	None	I
I/K	0.2627	likely_benign	0.2363	benign	-0.736	Destabilizing	0.018	N	0.323	neutral	None	None	None	None	I
I/L	0.0709	likely_benign	0.0701	benign	-0.571	Destabilizing	0.001	N	0.209	neutral	N	0.409676468	None	None	I
I/M	0.0728	likely_benign	0.0678	benign	-0.494	Destabilizing	0.196	N	0.303	neutral	N	0.49121763	None	None	I
I/N	0.1514	likely_benign	0.1309	benign	-0.519	Destabilizing	0.014	N	0.339	neutral	N	0.475440101	None	None	I
I/P	0.6941	likely_pathogenic	0.7201	pathogenic	-0.756	Destabilizing	0.037	N	0.318	neutral	None	None	None	None	I
I/Q	0.2491	likely_benign	0.2254	benign	-0.695	Destabilizing	0.085	N	0.427	neutral	None	None	None	None	I
I/R	0.197	likely_benign	0.1808	benign	-0.159	Destabilizing	0.044	N	0.369	neutral	None	None	None	None	I
I/S	0.1029	likely_benign	0.0963	benign	-1.12	Destabilizing	None	N	0.155	neutral	N	0.43247597	None	None	I
I/T	0.0458	likely_benign	0.0441	benign	-1.027	Destabilizing	None	N	0.135	neutral	N	0.327769948	None	None	I
I/V	0.0788	likely_benign	0.073	benign	-0.756	Destabilizing	0.001	N	0.13	neutral	N	0.428878305	None	None	I
I/W	0.6841	likely_pathogenic	0.6378	pathogenic	-0.872	Destabilizing	0.788	D	0.307	neutral	None	None	None	None	I
I/Y	0.422	ambiguous	0.3771	ambiguous	-0.653	Destabilizing	0.085	N	0.387	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.