TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	26144	78655;78656;78657	chr2:178567702;178567701;178567700	chr2:179432429;179432428;179432427
N2AB	24503	73732;73733;73734	chr2:178567702;178567701;178567700	chr2:179432429;179432428;179432427
N2A	23576	70951;70952;70953	chr2:178567702;178567701;178567700	chr2:179432429;179432428;179432427
N2B	17079	51460;51461;51462	chr2:178567702;178567701;178567700	chr2:179432429;179432428;179432427
Novex-1	17204	51835;51836;51837	chr2:178567702;178567701;178567700	chr2:179432429;179432428;179432427
Novex-2	17271	52036;52037;52038	chr2:178567702;178567701;178567700	chr2:179432429;179432428;179432427
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: Fn3-78
• Domain position: 57
• Structural Position: 83
• Q(SASA): 0.4689
• 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/M	rs759786276	-0.359	0.772	N	0.408	0.11	None	gnomAD-2.1.1	8.08E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	8.94E-06	0
I/M	rs759786276	-0.359	0.772	N	0.408	0.11	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	4.83E-05	0	0	0	0	None	0	0	0	0	0
I/M	rs759786276	-0.359	0.772	N	0.408	0.11	None	gnomAD-4.0.0	3.72256E-06	None	None	None	None	I	None	6.66773E-05	0	None	0	0	None	0	0	8.48679E-07	0	0
I/N	None	None	0.772	N	0.414	0.126	0.437527004654	gnomAD-4.0.0	6.85105E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.16031E-05	0
I/T	rs183015944	-0.651	0.001	N	0.144	0.106	None	gnomAD-2.1.1	1.69715E-04	None	None	None	None	I	None	1.29282E-04	3.48918E-04	None	0	1.11932E-04	None	6.88254E-04	None	4.67E-05	2.68E-05	1.67001E-04
I/T	rs183015944	-0.651	0.001	N	0.144	0.106	None	gnomAD-3.1.2	5.92E-05	None	None	None	None	I	None	1.20621E-04	0	0	0	0	None	9.42E-05	0	2.94E-05	2.07211E-04	0
I/T	rs183015944	-0.651	0.001	N	0.144	0.106	None	1000 genomes	1.99681E-04	None	None	None	None	I	None	8E-04	0	None	None	0	0	None	None	None	0	None
I/T	rs183015944	-0.651	0.001	N	0.144	0.106	None	gnomAD-4.0.0	6.20404E-05	None	None	None	None	I	None	9.33308E-05	2.00214E-04	None	0	6.70541E-05	None	4.69395E-05	0	1.7822E-05	5.71391E-04	3.20492E-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	0.2045	likely_benign	0.2668	benign	-0.595	Destabilizing	0.209	N	0.337	neutral	None	None	None	None	I
I/C	0.7807	likely_pathogenic	0.8042	pathogenic	-0.694	Destabilizing	0.991	D	0.356	neutral	None	None	None	None	I
I/D	0.8246	likely_pathogenic	0.8586	pathogenic	0.085	Stabilizing	0.561	D	0.42	neutral	None	None	None	None	I
I/E	0.6608	likely_pathogenic	0.7159	pathogenic	0.006	Stabilizing	0.39	N	0.368	neutral	None	None	None	None	I
I/F	0.2478	likely_benign	0.2721	benign	-0.537	Destabilizing	0.772	D	0.37	neutral	N	0.478447828	None	None	I
I/G	0.5757	likely_pathogenic	0.6574	pathogenic	-0.763	Destabilizing	0.561	D	0.408	neutral	None	None	None	None	I
I/H	0.615	likely_pathogenic	0.6598	pathogenic	-0.024	Destabilizing	0.972	D	0.367	neutral	None	None	None	None	I
I/K	0.4552	ambiguous	0.5154	ambiguous	-0.298	Destabilizing	0.004	N	0.281	neutral	None	None	None	None	I
I/L	0.0882	likely_benign	0.0927	benign	-0.275	Destabilizing	None	N	0.074	neutral	N	0.404488787	None	None	I
I/M	0.0841	likely_benign	0.0958	benign	-0.403	Destabilizing	0.772	D	0.408	neutral	N	0.504306278	None	None	I
I/N	0.3479	ambiguous	0.413	ambiguous	-0.142	Destabilizing	0.772	D	0.414	neutral	N	0.444871185	None	None	I
I/P	0.435	ambiguous	0.5034	ambiguous	-0.348	Destabilizing	0.901	D	0.411	neutral	None	None	None	None	I
I/Q	0.4518	ambiguous	0.5178	ambiguous	-0.326	Destabilizing	0.818	D	0.414	neutral	None	None	None	None	I
I/R	0.384	ambiguous	0.4161	ambiguous	0.206	Stabilizing	0.39	N	0.408	neutral	None	None	None	None	I
I/S	0.253	likely_benign	0.3163	benign	-0.643	Destabilizing	0.326	N	0.307	neutral	N	0.391730134	None	None	I
I/T	0.097	likely_benign	0.1399	benign	-0.61	Destabilizing	0.001	N	0.144	neutral	N	0.401696411	None	None	I
I/V	0.1037	likely_benign	0.129	benign	-0.348	Destabilizing	0.08	N	0.201	neutral	N	0.467865475	None	None	I
I/W	0.8129	likely_pathogenic	0.8055	pathogenic	-0.548	Destabilizing	0.991	D	0.401	neutral	None	None	None	None	I
I/Y	0.6822	likely_pathogenic	0.6849	pathogenic	-0.302	Destabilizing	0.965	D	0.389	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.