TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8329	25210;25211;25212	chr2:178718021;178718020;178718019	chr2:179582748;179582747;179582746
N2AB	8012	24259;24260;24261	chr2:178718021;178718020;178718019	chr2:179582748;179582747;179582746
N2A	7085	21478;21479;21480	chr2:178718021;178718020;178718019	chr2:179582748;179582747;179582746
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: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-68
• Domain position: 66
• Structural Position: 148
• Q(SASA): 0.541
• 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
S/G	None	None	0.008	N	0.089	0.191	0.15556083564	gnomAD-4.0.0	2.40064E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.625E-06	0	0
S/N	None	None	0.001	N	0.151	0.212	0.165133752707	gnomAD-4.0.0	4.78965E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	6.29665E-06	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
S/A	0.0862	likely_benign	0.0946	benign	-0.182	Destabilizing	None	N	0.082	neutral	None	None	None	None	I
S/C	0.169	likely_benign	0.2089	benign	-0.177	Destabilizing	0.988	D	0.343	neutral	D	0.532129779	None	None	I
S/D	0.3141	likely_benign	0.3587	ambiguous	-0.008	Destabilizing	0.673	D	0.184	neutral	None	None	None	None	I
S/E	0.491	ambiguous	0.5446	ambiguous	-0.109	Destabilizing	0.703	D	0.175	neutral	None	None	None	None	I
S/F	0.2552	likely_benign	0.2784	benign	-0.838	Destabilizing	0.991	D	0.362	neutral	None	None	None	None	I
S/G	0.0824	likely_benign	0.0947	benign	-0.272	Destabilizing	0.008	N	0.089	neutral	N	0.493949369	None	None	I
S/H	0.3177	likely_benign	0.364	ambiguous	-0.698	Destabilizing	0.991	D	0.345	neutral	None	None	None	None	I
S/I	0.1832	likely_benign	0.2173	benign	-0.078	Destabilizing	0.976	D	0.392	neutral	N	0.513772035	None	None	I
S/K	0.5766	likely_pathogenic	0.6405	pathogenic	-0.425	Destabilizing	0.08	N	0.091	neutral	None	None	None	None	I
S/L	0.1192	likely_benign	0.1268	benign	-0.078	Destabilizing	0.939	D	0.338	neutral	None	None	None	None	I
S/M	0.2246	likely_benign	0.2351	benign	0.079	Stabilizing	0.997	D	0.345	neutral	None	None	None	None	I
S/N	0.1013	likely_benign	0.1155	benign	-0.122	Destabilizing	0.001	N	0.151	neutral	N	0.495200163	None	None	I
S/P	0.3852	ambiguous	0.4666	ambiguous	-0.085	Destabilizing	0.893	D	0.387	neutral	None	None	None	None	I
S/Q	0.4515	ambiguous	0.5132	ambiguous	-0.367	Destabilizing	0.939	D	0.32	neutral	None	None	None	None	I
S/R	0.4545	ambiguous	0.5323	ambiguous	-0.164	Destabilizing	0.853	D	0.319	neutral	N	0.520423895	None	None	I
S/T	0.0889	likely_benign	0.093	benign	-0.207	Destabilizing	0.13	N	0.228	neutral	N	0.497624393	None	None	I
S/V	0.2047	likely_benign	0.2361	benign	-0.085	Destabilizing	0.742	D	0.334	neutral	None	None	None	None	I
S/W	0.3821	ambiguous	0.4258	ambiguous	-0.909	Destabilizing	0.999	D	0.423	neutral	None	None	None	None	I
S/Y	0.2446	likely_benign	0.2703	benign	-0.604	Destabilizing	0.997	D	0.363	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.