TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27195	81808;81809;81810	chr2:178564549;178564548;178564547	chr2:179429276;179429275;179429274
N2AB	25554	76885;76886;76887	chr2:178564549;178564548;178564547	chr2:179429276;179429275;179429274
N2A	24627	74104;74105;74106	chr2:178564549;178564548;178564547	chr2:179429276;179429275;179429274
N2B	18130	54613;54614;54615	chr2:178564549;178564548;178564547	chr2:179429276;179429275;179429274
Novex-1	18255	54988;54989;54990	chr2:178564549;178564548;178564547	chr2:179429276;179429275;179429274
Novex-2	18322	55189;55190;55191	chr2:178564549;178564548;178564547	chr2:179429276;179429275;179429274
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: A
• RefSeq wild type transcript codon: GCC
• RefSeq wild type template codon: CGG
• Domain: Fn3-86
• Domain position: 26
• Structural Position: 28
• Q(SASA): 0.4452
• 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
A/V	None	None	None	N	0.187	0.116	0.176091768786	gnomAD-4.0.0	1.59254E-06	None	None	None	None	I	None	0	0	None	0	2.78427E-05	None	0	0	0	0	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
A/C	0.4024	ambiguous	0.3853	ambiguous	-0.657	Destabilizing	0.824	D	0.324	neutral	None	None	None	None	I
A/D	0.177	likely_benign	0.1599	benign	-0.918	Destabilizing	0.062	N	0.356	neutral	N	0.417778664	None	None	I
A/E	0.1196	likely_benign	0.1124	benign	-1.07	Destabilizing	None	N	0.161	neutral	None	None	None	None	I
A/F	0.2495	likely_benign	0.2122	benign	-0.996	Destabilizing	0.38	N	0.415	neutral	None	None	None	None	I
A/G	0.1426	likely_benign	0.1317	benign	-0.454	Destabilizing	0.117	N	0.235	neutral	N	0.413604995	None	None	I
A/H	0.35	ambiguous	0.335	benign	-0.523	Destabilizing	0.555	D	0.395	neutral	None	None	None	None	I
A/I	0.1186	likely_benign	0.1038	benign	-0.422	Destabilizing	0.029	N	0.324	neutral	None	None	None	None	I
A/K	0.2779	likely_benign	0.2522	benign	-0.872	Destabilizing	0.081	N	0.276	neutral	None	None	None	None	I
A/L	0.1042	likely_benign	0.0932	benign	-0.422	Destabilizing	0.081	N	0.273	neutral	None	None	None	None	I
A/M	0.1504	likely_benign	0.1336	benign	-0.427	Destabilizing	0.38	N	0.307	neutral	None	None	None	None	I
A/N	0.1534	likely_benign	0.1402	benign	-0.443	Destabilizing	0.38	N	0.403	neutral	None	None	None	None	I
A/P	0.2009	likely_benign	0.1836	benign	-0.379	Destabilizing	0.484	N	0.329	neutral	N	0.437807219	None	None	I
A/Q	0.1867	likely_benign	0.185	benign	-0.758	Destabilizing	0.007	N	0.213	neutral	None	None	None	None	I
A/R	0.2787	likely_benign	0.2544	benign	-0.324	Destabilizing	0.149	N	0.344	neutral	None	None	None	None	I
A/S	0.0846	likely_benign	0.0831	benign	-0.568	Destabilizing	0.052	N	0.265	neutral	N	0.433228119	None	None	I
A/T	0.0703	likely_benign	0.0694	benign	-0.655	Destabilizing	0.062	N	0.256	neutral	N	0.415277076	None	None	I
A/V	0.0798	likely_benign	0.0719	benign	-0.379	Destabilizing	None	N	0.187	neutral	N	0.428246373	None	None	I
A/W	0.6386	likely_pathogenic	0.5931	pathogenic	-1.151	Destabilizing	0.935	D	0.514	neutral	None	None	None	None	I
A/Y	0.3635	ambiguous	0.3335	benign	-0.822	Destabilizing	0.555	D	0.419	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.