TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16741	50446;50447;50448	chr2:178612304;178612303;178612302	chr2:179477031;179477030;179477029
N2AB	15100	45523;45524;45525	chr2:178612304;178612303;178612302	chr2:179477031;179477030;179477029
N2A	14173	42742;42743;42744	chr2:178612304;178612303;178612302	chr2:179477031;179477030;179477029
N2B	7676	23251;23252;23253	chr2:178612304;178612303;178612302	chr2:179477031;179477030;179477029
Novex-1	7801	23626;23627;23628	chr2:178612304;178612303;178612302	chr2:179477031;179477030;179477029
Novex-2	7868	23827;23828;23829	chr2:178612304;178612303;178612302	chr2:179477031;179477030;179477029
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Fn3-9
• Domain position: 91
• Structural Position: 125
• Q(SASA): 0.7865
• 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
D/E	rs372658275	None	0.999	N	0.503	0.159	0.258283824007	gnomAD-3.1.2	1.97E-05	None	None	None	None	I	None	4.83E-05	6.55E-05	0	0	0	None	0	0	0	0	0
D/E	rs372658275	None	0.999	N	0.503	0.159	0.258283824007	gnomAD-4.0.0	3.10078E-06	None	None	None	None	I	None	4.00866E-05	1.66911E-05	None	0	0	None	0	0	0	0	1.60292E-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
D/A	0.7457	likely_pathogenic	0.7645	pathogenic	0.059	Stabilizing	1.0	D	0.717	prob.delet.	N	0.500598107	None	None	I
D/C	0.9748	likely_pathogenic	0.9792	pathogenic	-0.208	Destabilizing	1.0	D	0.687	prob.delet.	None	None	None	None	I
D/E	0.537	ambiguous	0.5567	ambiguous	-0.272	Destabilizing	0.999	D	0.503	neutral	N	0.431696693	None	None	I
D/F	0.9551	likely_pathogenic	0.9605	pathogenic	0.014	Stabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	I
D/G	0.6106	likely_pathogenic	0.6261	pathogenic	-0.058	Destabilizing	1.0	D	0.75	deleterious	N	0.494408467	None	None	I
D/H	0.8935	likely_pathogenic	0.8899	pathogenic	0.646	Stabilizing	1.0	D	0.711	prob.delet.	D	0.598351881	None	None	I
D/I	0.9259	likely_pathogenic	0.9408	pathogenic	0.3	Stabilizing	1.0	D	0.699	prob.delet.	None	None	None	None	I
D/K	0.9051	likely_pathogenic	0.9061	pathogenic	0.41	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
D/L	0.9146	likely_pathogenic	0.9264	pathogenic	0.3	Stabilizing	1.0	D	0.733	deleterious	None	None	None	None	I
D/M	0.9668	likely_pathogenic	0.975	pathogenic	0.037	Stabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	I
D/N	0.4201	ambiguous	0.4021	ambiguous	0.136	Stabilizing	1.0	D	0.739	deleterious	N	0.493892155	None	None	I
D/P	0.9676	likely_pathogenic	0.9676	pathogenic	0.239	Stabilizing	1.0	D	0.724	deleterious	None	None	None	None	I
D/Q	0.8835	likely_pathogenic	0.895	pathogenic	0.15	Stabilizing	1.0	D	0.695	prob.delet.	None	None	None	None	I
D/R	0.9241	likely_pathogenic	0.9287	pathogenic	0.67	Stabilizing	1.0	D	0.707	prob.delet.	None	None	None	None	I
D/S	0.608	likely_pathogenic	0.6177	pathogenic	0.041	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
D/T	0.7918	likely_pathogenic	0.8128	pathogenic	0.142	Stabilizing	1.0	D	0.779	deleterious	None	None	None	None	I
D/V	0.8213	likely_pathogenic	0.8469	pathogenic	0.239	Stabilizing	1.0	D	0.721	deleterious	D	0.541001901	None	None	I
D/W	0.9902	likely_pathogenic	0.9922	pathogenic	0.057	Stabilizing	1.0	D	0.633	neutral	None	None	None	None	I
D/Y	0.7637	likely_pathogenic	0.7876	pathogenic	0.24	Stabilizing	1.0	D	0.707	prob.delet.	D	0.638770578	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.