TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33341	100246;100247;100248	chr2:178537088;178537087;178537086	chr2:179401815;179401814;179401813
N2AB	31700	95323;95324;95325	chr2:178537088;178537087;178537086	chr2:179401815;179401814;179401813
N2A	30773	92542;92543;92544	chr2:178537088;178537087;178537086	chr2:179401815;179401814;179401813
N2B	24276	73051;73052;73053	chr2:178537088;178537087;178537086	chr2:179401815;179401814;179401813
Novex-1	24401	73426;73427;73428	chr2:178537088;178537087;178537086	chr2:179401815;179401814;179401813
Novex-2	24468	73627;73628;73629	chr2:178537088;178537087;178537086	chr2:179401815;179401814;179401813
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Fn3-130
• Domain position: 52
• Structural Position: 67
• Q(SASA): 0.4555
• 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
L/S	None	None	1.0	N	0.811	0.532	0.641048165634	gnomAD-4.0.0	1.59263E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85979E-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
L/A	0.5092	ambiguous	0.532	ambiguous	-1.195	Destabilizing	0.999	D	0.702	prob.neutral	None	None	None	None	I
L/C	0.7796	likely_pathogenic	0.7661	pathogenic	-0.731	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
L/D	0.9276	likely_pathogenic	0.9271	pathogenic	-0.491	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	I
L/E	0.6588	likely_pathogenic	0.6512	pathogenic	-0.545	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	I
L/F	0.5341	ambiguous	0.4788	ambiguous	-0.916	Destabilizing	1.0	D	0.705	prob.neutral	N	0.492583067	None	None	I
L/G	0.8678	likely_pathogenic	0.8758	pathogenic	-1.442	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
L/H	0.6608	likely_pathogenic	0.6075	pathogenic	-0.61	Destabilizing	1.0	D	0.776	deleterious	None	None	None	None	I
L/I	0.1706	likely_benign	0.1584	benign	-0.629	Destabilizing	0.999	D	0.45	neutral	None	None	None	None	I
L/K	0.4589	ambiguous	0.4709	ambiguous	-0.725	Destabilizing	1.0	D	0.804	deleterious	None	None	None	None	I
L/M	0.2134	likely_benign	0.1896	benign	-0.488	Destabilizing	1.0	D	0.665	neutral	N	0.446618703	None	None	I
L/N	0.7054	likely_pathogenic	0.7278	pathogenic	-0.471	Destabilizing	1.0	D	0.799	deleterious	None	None	None	None	I
L/P	0.5053	ambiguous	0.5268	ambiguous	-0.784	Destabilizing	1.0	D	0.801	deleterious	None	None	None	None	I
L/Q	0.4294	ambiguous	0.3911	ambiguous	-0.705	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
L/R	0.4738	ambiguous	0.428	ambiguous	-0.099	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
L/S	0.7366	likely_pathogenic	0.7521	pathogenic	-1.038	Destabilizing	1.0	D	0.811	deleterious	N	0.468511341	None	None	I
L/T	0.4047	ambiguous	0.4414	ambiguous	-0.982	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	I
L/V	0.1836	likely_benign	0.1675	benign	-0.784	Destabilizing	0.999	D	0.514	neutral	N	0.429243664	None	None	I
L/W	0.7851	likely_pathogenic	0.7138	pathogenic	-0.916	Destabilizing	1.0	D	0.767	deleterious	N	0.47881107	None	None	I
L/Y	0.8022	likely_pathogenic	0.7709	pathogenic	-0.701	Destabilizing	1.0	D	0.807	deleterious	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.