TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8669	26230;26231;26232	chr2:178715181;178715180;178715179	chr2:179579908;179579907;179579906
N2AB	8352	25279;25280;25281	chr2:178715181;178715180;178715179	chr2:179579908;179579907;179579906
N2A	7425	22498;22499;22500	chr2:178715181;178715180;178715179	chr2:179579908;179579907;179579906
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: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-72
• Domain position: 27
• Structural Position: 41
• Q(SASA): 0.6631
• 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
T/I	rs773386252	0.103	0.998	N	0.667	0.403	0.579560680208	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	0	1.65618E-04
T/S	rs773386252	-0.288	0.157	N	0.295	0.084	0.202949470691	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.87E-06	0
T/S	rs773386252	-0.288	0.157	N	0.295	0.084	0.202949470691	gnomAD-4.0.0	1.59147E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85894E-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
T/A	0.3216	likely_benign	0.2564	benign	-0.4	Destabilizing	0.497	N	0.549	neutral	N	0.508507816	None	None	I
T/C	0.8529	likely_pathogenic	0.8223	pathogenic	-0.521	Destabilizing	1.0	D	0.657	neutral	None	None	None	None	I
T/D	0.7324	likely_pathogenic	0.6293	pathogenic	0.185	Stabilizing	0.986	D	0.605	neutral	None	None	None	None	I
T/E	0.6877	likely_pathogenic	0.5792	pathogenic	0.16	Stabilizing	0.996	D	0.614	neutral	None	None	None	None	I
T/F	0.5657	likely_pathogenic	0.4595	ambiguous	-0.847	Destabilizing	1.0	D	0.703	prob.neutral	None	None	None	None	I
T/G	0.6542	likely_pathogenic	0.5838	pathogenic	-0.555	Destabilizing	0.994	D	0.648	neutral	None	None	None	None	I
T/H	0.5453	ambiguous	0.4614	ambiguous	-0.573	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
T/I	0.6004	likely_pathogenic	0.4865	ambiguous	-0.101	Destabilizing	0.998	D	0.667	neutral	N	0.506931736	None	None	I
T/K	0.602	likely_pathogenic	0.4949	ambiguous	-0.295	Destabilizing	0.997	D	0.61	neutral	None	None	None	None	I
T/L	0.3091	likely_benign	0.2572	benign	-0.101	Destabilizing	0.995	D	0.655	neutral	None	None	None	None	I
T/M	0.1817	likely_benign	0.1647	benign	-0.34	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	I
T/N	0.276	likely_benign	0.2352	benign	-0.295	Destabilizing	0.981	D	0.625	neutral	N	0.481571931	None	None	I
T/P	0.6838	likely_pathogenic	0.5505	ambiguous	-0.172	Destabilizing	0.991	D	0.667	neutral	N	0.496456885	None	None	I
T/Q	0.5451	ambiguous	0.458	ambiguous	-0.387	Destabilizing	0.997	D	0.661	neutral	None	None	None	None	I
T/R	0.5549	ambiguous	0.4562	ambiguous	-0.012	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	I
T/S	0.169	likely_benign	0.155	benign	-0.514	Destabilizing	0.157	N	0.295	neutral	N	0.452038458	None	None	I
T/V	0.5063	ambiguous	0.4003	ambiguous	-0.172	Destabilizing	0.992	D	0.646	neutral	None	None	None	None	I
T/W	0.8494	likely_pathogenic	0.7855	pathogenic	-0.917	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
T/Y	0.5883	likely_pathogenic	0.4868	ambiguous	-0.589	Destabilizing	1.0	D	0.704	prob.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.