TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30640	92143;92144;92145	chr2:178549804;178549803;178549802	chr2:179414531;179414530;179414529
N2AB	28999	87220;87221;87222	chr2:178549804;178549803;178549802	chr2:179414531;179414530;179414529
N2A	28072	84439;84440;84441	chr2:178549804;178549803;178549802	chr2:179414531;179414530;179414529
N2B	21575	64948;64949;64950	chr2:178549804;178549803;178549802	chr2:179414531;179414530;179414529
Novex-1	21700	65323;65324;65325	chr2:178549804;178549803;178549802	chr2:179414531;179414530;179414529
Novex-2	21767	65524;65525;65526	chr2:178549804;178549803;178549802	chr2:179414531;179414530;179414529
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Fn3-111
• Domain position: 22
• Structural Position: 23
• Q(SASA): 0.6352
• 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
W/S	None	None	1.0	N	0.745	0.387	0.551798466036	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93751E-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
W/A	0.3874	ambiguous	0.5221	ambiguous	-2.632	Highly Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	N
W/C	0.5316	ambiguous	0.6794	pathogenic	-1.042	Destabilizing	1.0	D	0.764	deleterious	N	0.439519373	None	None	N
W/D	0.8316	likely_pathogenic	0.9164	pathogenic	-1.066	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
W/E	0.7533	likely_pathogenic	0.859	pathogenic	-0.981	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
W/F	0.2263	likely_benign	0.285	benign	-1.465	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
W/G	0.3429	ambiguous	0.4894	ambiguous	-2.836	Highly Destabilizing	1.0	D	0.667	neutral	N	0.43191861	None	None	N
W/H	0.4795	ambiguous	0.5827	pathogenic	-1.186	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
W/I	0.527	ambiguous	0.6391	pathogenic	-1.913	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
W/K	0.7483	likely_pathogenic	0.8605	pathogenic	-1.232	Destabilizing	1.0	D	0.754	deleterious	None	None	None	None	N
W/L	0.3295	likely_benign	0.4366	ambiguous	-1.913	Destabilizing	1.0	D	0.667	neutral	N	0.434977558	None	None	N
W/M	0.5381	ambiguous	0.646	pathogenic	-1.427	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
W/N	0.6849	likely_pathogenic	0.8033	pathogenic	-1.54	Destabilizing	1.0	D	0.757	deleterious	None	None	None	None	N
W/P	0.9928	likely_pathogenic	0.9957	pathogenic	-2.166	Highly Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
W/Q	0.5733	likely_pathogenic	0.7326	pathogenic	-1.515	Destabilizing	1.0	D	0.759	deleterious	None	None	None	None	N
W/R	0.6046	likely_pathogenic	0.7653	pathogenic	-0.737	Destabilizing	1.0	D	0.767	deleterious	N	0.382143151	None	None	N
W/S	0.2176	likely_benign	0.3209	benign	-2.041	Highly Destabilizing	1.0	D	0.745	deleterious	N	0.291153	None	None	N
W/T	0.3365	likely_benign	0.4537	ambiguous	-1.914	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	N
W/V	0.4573	ambiguous	0.5799	pathogenic	-2.166	Highly Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	N
W/Y	0.3348	likely_benign	0.4186	ambiguous	-1.267	Destabilizing	1.0	D	0.683	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.