TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23595	71008;71009;71010	chr2:178575349;178575348;178575347	chr2:179440076;179440075;179440074
N2AB	21954	66085;66086;66087	chr2:178575349;178575348;178575347	chr2:179440076;179440075;179440074
N2A	21027	63304;63305;63306	chr2:178575349;178575348;178575347	chr2:179440076;179440075;179440074
N2B	14530	43813;43814;43815	chr2:178575349;178575348;178575347	chr2:179440076;179440075;179440074
Novex-1	14655	44188;44189;44190	chr2:178575349;178575348;178575347	chr2:179440076;179440075;179440074
Novex-2	14722	44389;44390;44391	chr2:178575349;178575348;178575347	chr2:179440076;179440075;179440074
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTA
• RefSeq wild type template codon: GAT
• Domain: Fn3-59
• Domain position: 64
• Structural Position: 97
• Q(SASA): 0.1269
• 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
L/P	rs886055249	-1.718	0.998	D	0.833	0.861	0.916108489367	gnomAD-2.1.1	4.02E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.89E-06	0
L/P	rs886055249	-1.718	0.998	D	0.833	0.861	0.916108489367	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
L/P	rs886055249	-1.718	0.998	D	0.833	0.861	0.916108489367	gnomAD-4.0.0	6.4075E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.19683E-05	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
L/A	0.9069	likely_pathogenic	0.8919	pathogenic	-2.353	Highly Destabilizing	0.969	D	0.788	deleterious	None	None	None	None	N
L/C	0.8079	likely_pathogenic	0.8045	pathogenic	-1.868	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9986	pathogenic	-1.663	Destabilizing	0.996	D	0.831	deleterious	None	None	None	None	N
L/E	0.9929	likely_pathogenic	0.9912	pathogenic	-1.534	Destabilizing	0.994	D	0.811	deleterious	None	None	None	None	N
L/F	0.8507	likely_pathogenic	0.8091	pathogenic	-1.598	Destabilizing	0.957	D	0.885	deleterious	None	None	None	None	N
L/G	0.9784	likely_pathogenic	0.9762	pathogenic	-2.817	Highly Destabilizing	0.996	D	0.814	deleterious	None	None	None	None	N
L/H	0.9843	likely_pathogenic	0.9814	pathogenic	-1.965	Destabilizing	0.994	D	0.838	deleterious	None	None	None	None	N
L/I	0.4252	ambiguous	0.3291	benign	-1.07	Destabilizing	0.412	N	0.82	deleterious	D	0.635410968	None	None	N
L/K	0.9869	likely_pathogenic	0.9849	pathogenic	-1.624	Destabilizing	0.765	D	0.808	deleterious	None	None	None	None	N
L/M	0.4105	ambiguous	0.3621	ambiguous	-1.011	Destabilizing	0.988	D	0.847	deleterious	None	None	None	None	N
L/N	0.9876	likely_pathogenic	0.9859	pathogenic	-1.699	Destabilizing	0.996	D	0.828	deleterious	None	None	None	None	N
L/P	0.9935	likely_pathogenic	0.9917	pathogenic	-1.472	Destabilizing	0.998	D	0.833	deleterious	D	0.674605715	None	None	N
L/Q	0.9633	likely_pathogenic	0.9534	pathogenic	-1.71	Destabilizing	0.986	D	0.825	deleterious	D	0.642566994	None	None	N
L/R	0.9712	likely_pathogenic	0.9677	pathogenic	-1.162	Destabilizing	0.985	D	0.807	deleterious	D	0.649299768	None	None	N
L/S	0.9877	likely_pathogenic	0.9848	pathogenic	-2.533	Highly Destabilizing	0.991	D	0.802	deleterious	None	None	None	None	N
L/T	0.9351	likely_pathogenic	0.9239	pathogenic	-2.252	Highly Destabilizing	0.985	D	0.827	deleterious	None	None	None	None	N
L/V	0.4126	ambiguous	0.335	benign	-1.472	Destabilizing	0.48	N	0.829	deleterious	D	0.597214524	None	None	N
L/W	0.9842	likely_pathogenic	0.9793	pathogenic	-1.71	Destabilizing	0.999	D	0.803	deleterious	None	None	None	None	N
L/Y	0.9824	likely_pathogenic	0.9776	pathogenic	-1.478	Destabilizing	0.011	N	0.688	prob.neutral	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.