TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8277	25054;25055;25056	chr2:178718177;178718176;178718175	chr2:179582904;179582903;179582902
N2AB	7960	24103;24104;24105	chr2:178718177;178718176;178718175	chr2:179582904;179582903;179582902
N2A	7033	21322;21323;21324	chr2:178718177;178718176;178718175	chr2:179582904;179582903;179582902
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
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: Ig-68
• Domain position: 14
• Structural Position: 23
• Q(SASA): 0.7584
• 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/T	rs745818162	-0.48	0.074	N	0.383	0.135	0.527404433557	gnomAD-2.1.1	1.1E-05	None	None	None	None	I	None	0	0	None	0	5.14E-05	None	0	None	5.09E-05	7.83E-06	0
I/T	rs745818162	-0.48	0.074	N	0.383	0.135	0.527404433557	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	2.07039E-04	0
I/T	rs745818162	-0.48	0.074	N	0.383	0.135	0.527404433557	gnomAD-4.0.0	7.7693E-06	None	None	None	None	I	None	0	0	None	0	7.27237E-05	None	0	0	2.39584E-06	1.3416E-05	2.85063E-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	0.1295	likely_benign	0.1315	benign	-1.336	Destabilizing	0.126	N	0.373	neutral	None	None	None	None	I
I/C	0.6555	likely_pathogenic	0.6619	pathogenic	-0.581	Destabilizing	0.833	D	0.326	neutral	None	None	None	None	I
I/D	0.4674	ambiguous	0.4922	ambiguous	-1.017	Destabilizing	0.833	D	0.402	neutral	None	None	None	None	I
I/E	0.3246	likely_benign	0.3318	benign	-1.053	Destabilizing	0.786	D	0.415	neutral	None	None	None	None	I
I/F	0.1341	likely_benign	0.1417	benign	-1.036	Destabilizing	0.001	N	0.129	neutral	N	0.484909542	None	None	I
I/G	0.4988	ambiguous	0.5021	ambiguous	-1.606	Destabilizing	0.587	D	0.425	neutral	None	None	None	None	I
I/H	0.4197	ambiguous	0.4398	ambiguous	-0.892	Destabilizing	0.96	D	0.346	neutral	None	None	None	None	I
I/K	0.2799	likely_benign	0.303	benign	-0.929	Destabilizing	0.04	N	0.423	neutral	None	None	None	None	I
I/L	0.0979	likely_benign	0.0862	benign	-0.685	Destabilizing	None	N	0.11	neutral	N	0.478166267	None	None	I
I/M	0.0893	likely_benign	0.0821	benign	-0.459	Destabilizing	0.181	N	0.354	neutral	N	0.51583922	None	None	I
I/N	0.227	likely_benign	0.2339	benign	-0.615	Destabilizing	0.92	D	0.382	neutral	N	0.499544304	None	None	I
I/P	0.3116	likely_benign	0.3092	benign	-0.87	Destabilizing	0.938	D	0.395	neutral	None	None	None	None	I
I/Q	0.3004	likely_benign	0.3093	benign	-0.833	Destabilizing	0.863	D	0.371	neutral	None	None	None	None	I
I/R	0.1951	likely_benign	0.2181	benign	-0.302	Destabilizing	0.664	D	0.384	neutral	None	None	None	None	I
I/S	0.1751	likely_benign	0.1803	benign	-1.089	Destabilizing	0.346	N	0.403	neutral	N	0.494327798	None	None	I
I/T	0.0905	likely_benign	0.089	benign	-1.018	Destabilizing	0.074	N	0.383	neutral	N	0.496482669	None	None	I
I/V	0.075	likely_benign	0.0716	benign	-0.87	Destabilizing	None	N	0.101	neutral	N	0.413247996	None	None	I
I/W	0.6085	likely_pathogenic	0.6411	pathogenic	-1.107	Destabilizing	0.988	D	0.349	neutral	None	None	None	None	I
I/Y	0.4503	ambiguous	0.4663	ambiguous	-0.895	Destabilizing	0.016	N	0.408	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.