TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34166	102721;102722;102723	chr2:178534119;178534118;178534117	chr2:179398846;179398845;179398844
N2AB	32525	97798;97799;97800	chr2:178534119;178534118;178534117	chr2:179398846;179398845;179398844
N2A	31598	95017;95018;95019	chr2:178534119;178534118;178534117	chr2:179398846;179398845;179398844
N2B	25101	75526;75527;75528	chr2:178534119;178534118;178534117	chr2:179398846;179398845;179398844
Novex-1	25226	75901;75902;75903	chr2:178534119;178534118;178534117	chr2:179398846;179398845;179398844
Novex-2	25293	76102;76103;76104	chr2:178534119;178534118;178534117	chr2:179398846;179398845;179398844
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Ig-160
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.1376
• Predicted PPI site: N

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
T/S	None	None	0.999	N	0.624	0.427	0.394079506076	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-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
T/A	0.3797	ambiguous	0.3489	ambiguous	-1.04	Destabilizing	0.999	D	0.589	neutral	N	0.443610976	None	None	N
T/C	0.8375	likely_pathogenic	0.8551	pathogenic	-0.877	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
T/D	0.9591	likely_pathogenic	0.9539	pathogenic	-1.409	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
T/E	0.9176	likely_pathogenic	0.912	pathogenic	-1.235	Destabilizing	1.0	D	0.783	deleterious	None	None	None	None	N
T/F	0.949	likely_pathogenic	0.9386	pathogenic	-0.868	Destabilizing	1.0	D	0.787	deleterious	None	None	None	None	N
T/G	0.8398	likely_pathogenic	0.8376	pathogenic	-1.448	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	N
T/H	0.9162	likely_pathogenic	0.9066	pathogenic	-1.745	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
T/I	0.7742	likely_pathogenic	0.734	pathogenic	0.014	Stabilizing	1.0	D	0.817	deleterious	N	0.486631034	None	None	N
T/K	0.8895	likely_pathogenic	0.8845	pathogenic	-0.671	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
T/L	0.5835	likely_pathogenic	0.5327	ambiguous	0.014	Stabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	N
T/M	0.4896	ambiguous	0.4446	ambiguous	0.084	Stabilizing	1.0	D	0.766	deleterious	None	None	None	None	N
T/N	0.7869	likely_pathogenic	0.766	pathogenic	-1.338	Destabilizing	1.0	D	0.763	deleterious	D	0.525112065	None	None	N
T/P	0.7635	likely_pathogenic	0.7661	pathogenic	-0.304	Destabilizing	1.0	D	0.813	deleterious	N	0.364813757	None	None	N
T/Q	0.8775	likely_pathogenic	0.8689	pathogenic	-1.146	Destabilizing	1.0	D	0.81	deleterious	None	None	None	None	N
T/R	0.8624	likely_pathogenic	0.8501	pathogenic	-0.852	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
T/S	0.4611	ambiguous	0.4388	ambiguous	-1.524	Destabilizing	0.999	D	0.624	neutral	N	0.476550113	None	None	N
T/V	0.5518	ambiguous	0.5133	ambiguous	-0.304	Destabilizing	0.999	D	0.675	neutral	None	None	None	None	N
T/W	0.9861	likely_pathogenic	0.9835	pathogenic	-1.019	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	N
T/Y	0.9531	likely_pathogenic	0.9436	pathogenic	-0.634	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N

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.