TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15254	45985;45986;45987	chr2:178620850;178620849;178620848	chr2:179485577;179485576;179485575
N2AB	13613	41062;41063;41064	chr2:178620850;178620849;178620848	chr2:179485577;179485576;179485575
N2A	12686	38281;38282;38283	chr2:178620850;178620849;178620848	chr2:179485577;179485576;179485575
N2B	6189	18790;18791;18792	chr2:178620850;178620849;178620848	chr2:179485577;179485576;179485575
Novex-1	6314	19165;19166;19167	chr2:178620850;178620849;178620848	chr2:179485577;179485576;179485575
Novex-2	6381	19366;19367;19368	chr2:178620850;178620849;178620848	chr2:179485577;179485576;179485575
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Ig-104
• Domain position: 47
• Structural Position: 122
• Q(SASA): 0.3164
• 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/F	rs72677226	-1.073	0.988	D	0.391	0.254	0.710200110468	gnomAD-2.1.1	1.21199E-04	None	None	None	None	I	None	6.47E-05	8.4268E-04	None	0	0	None	0	None	0	0	0
I/F	rs72677226	-1.073	0.988	D	0.391	0.254	0.710200110468	gnomAD-3.1.2	3.29E-05	None	None	None	None	I	None	4.83E-05	1.96876E-04	0	0	0	None	0	0	0	0	0
I/F	rs72677226	-1.073	0.988	D	0.391	0.254	0.710200110468	gnomAD-4.0.0	5.13194E-05	None	None	None	None	I	None	3.38972E-05	5.94167E-04	None	0	0	None	0	0	0	0	8.54896E-05
I/M	None	None	0.988	N	0.438	0.286	0.506552580704	gnomAD-4.0.0	1.59356E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.86259E-06	0	0
I/N	rs2058156310	None	0.988	N	0.526	0.552	0.842181085062	gnomAD-3.1.2	6.6E-06	None	None	None	None	I	None	0	6.57E-05	0	0	0	None	0	0	0	0	0
I/N	rs2058156310	None	0.988	N	0.526	0.552	0.842181085062	gnomAD-4.0.0	6.5957E-06	None	None	None	None	I	None	0	6.57289E-05	None	0	0	None	0	0	0	0	0
I/V	rs72677226	-0.823	0.238	N	0.143	0.07	0.51759925163	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs72677226	-0.823	0.238	N	0.143	0.07	0.51759925163	gnomAD-4.0.0	1.59356E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43336E-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
I/A	0.4097	ambiguous	0.5162	ambiguous	-2.206	Highly Destabilizing	0.864	D	0.332	neutral	None	None	None	None	I
I/C	0.7287	likely_pathogenic	0.7696	pathogenic	-1.737	Destabilizing	1.0	D	0.459	neutral	None	None	None	None	I
I/D	0.736	likely_pathogenic	0.7939	pathogenic	-1.949	Destabilizing	0.991	D	0.503	neutral	None	None	None	None	I
I/E	0.6061	likely_pathogenic	0.6693	pathogenic	-1.863	Destabilizing	0.991	D	0.479	neutral	None	None	None	None	I
I/F	0.2116	likely_benign	0.2624	benign	-1.451	Destabilizing	0.988	D	0.391	neutral	D	0.528805663	None	None	I
I/G	0.7155	likely_pathogenic	0.7975	pathogenic	-2.608	Highly Destabilizing	0.991	D	0.453	neutral	None	None	None	None	I
I/H	0.4916	ambiguous	0.5717	pathogenic	-1.791	Destabilizing	1.0	D	0.525	neutral	None	None	None	None	I
I/K	0.4149	ambiguous	0.4712	ambiguous	-1.539	Destabilizing	0.991	D	0.472	neutral	None	None	None	None	I
I/L	0.1448	likely_benign	0.1636	benign	-1.116	Destabilizing	0.03	N	0.127	neutral	N	0.497054773	None	None	I
I/M	0.1145	likely_benign	0.1352	benign	-1.111	Destabilizing	0.988	D	0.438	neutral	N	0.506712697	None	None	I
I/N	0.2981	likely_benign	0.3736	ambiguous	-1.533	Destabilizing	0.988	D	0.526	neutral	N	0.503278922	None	None	I
I/P	0.9476	likely_pathogenic	0.9618	pathogenic	-1.453	Destabilizing	0.995	D	0.524	neutral	None	None	None	None	I
I/Q	0.4348	ambiguous	0.502	ambiguous	-1.642	Destabilizing	0.995	D	0.525	neutral	None	None	None	None	I
I/R	0.3117	likely_benign	0.3521	ambiguous	-1.04	Destabilizing	0.995	D	0.531	neutral	None	None	None	None	I
I/S	0.3148	likely_benign	0.3895	ambiguous	-2.253	Highly Destabilizing	0.677	D	0.295	neutral	N	0.487356433	None	None	I
I/T	0.2625	likely_benign	0.353	ambiguous	-2.042	Highly Destabilizing	0.921	D	0.318	neutral	N	0.492924332	None	None	I
I/V	0.0773	likely_benign	0.1008	benign	-1.453	Destabilizing	0.238	N	0.143	neutral	N	0.441841628	None	None	I
I/W	0.8131	likely_pathogenic	0.8339	pathogenic	-1.568	Destabilizing	1.0	D	0.596	neutral	None	None	None	None	I
I/Y	0.5354	ambiguous	0.581	pathogenic	-1.342	Destabilizing	0.999	D	0.461	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.