TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22573	67942;67943;67944	chr2:178579313;178579312;178579311	chr2:179444040;179444039;179444038
N2AB	20932	63019;63020;63021	chr2:178579313;178579312;178579311	chr2:179444040;179444039;179444038
N2A	20005	60238;60239;60240	chr2:178579313;178579312;178579311	chr2:179444040;179444039;179444038
N2B	13508	40747;40748;40749	chr2:178579313;178579312;178579311	chr2:179444040;179444039;179444038
Novex-1	13633	41122;41123;41124	chr2:178579313;178579312;178579311	chr2:179444040;179444039;179444038
Novex-2	13700	41323;41324;41325	chr2:178579313;178579312;178579311	chr2:179444040;179444039;179444038
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Ig-127
• Domain position: 14
• Structural Position: 34
• Q(SASA): 0.5244
• 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
P/S	rs767245563	-0.375	1.0	D	0.749	0.385	0.482721949076	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	0	None	1.0012E-04	0	None	0	None	0	0	0
P/S	rs767245563	-0.375	1.0	D	0.749	0.385	0.482721949076	gnomAD-4.0.0	1.60013E-06	None	None	None	None	I	None	0	0	None	4.78469E-05	0	None	0	0	0	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
P/A	0.2338	likely_benign	0.192	benign	-0.739	Destabilizing	1.0	D	0.703	prob.neutral	N	0.487374623	None	None	I
P/C	0.8327	likely_pathogenic	0.8124	pathogenic	-0.675	Destabilizing	1.0	D	0.701	prob.neutral	None	None	None	None	I
P/D	0.8506	likely_pathogenic	0.788	pathogenic	-0.713	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
P/E	0.7405	likely_pathogenic	0.6523	pathogenic	-0.8	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
P/F	0.8675	likely_pathogenic	0.8189	pathogenic	-0.784	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	I
P/G	0.6833	likely_pathogenic	0.6105	pathogenic	-0.916	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	I
P/H	0.6218	likely_pathogenic	0.5579	ambiguous	-0.42	Destabilizing	1.0	D	0.691	prob.neutral	N	0.499998376	None	None	I
P/I	0.6748	likely_pathogenic	0.6234	pathogenic	-0.402	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
P/K	0.767	likely_pathogenic	0.6905	pathogenic	-0.776	Destabilizing	1.0	D	0.731	prob.delet.	None	None	None	None	I
P/L	0.3304	likely_benign	0.2801	benign	-0.402	Destabilizing	1.0	D	0.737	prob.delet.	N	0.50321438	None	None	I
P/M	0.6944	likely_pathogenic	0.6326	pathogenic	-0.44	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
P/N	0.7357	likely_pathogenic	0.6676	pathogenic	-0.515	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
P/Q	0.5348	ambiguous	0.4465	ambiguous	-0.751	Destabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
P/R	0.5797	likely_pathogenic	0.5	ambiguous	-0.192	Destabilizing	1.0	D	0.744	deleterious	N	0.521762328	None	None	I
P/S	0.3939	ambiguous	0.3306	benign	-0.859	Destabilizing	1.0	D	0.749	deleterious	D	0.530112453	None	None	I
P/T	0.3578	ambiguous	0.3087	benign	-0.848	Destabilizing	1.0	D	0.739	prob.delet.	N	0.477838289	None	None	I
P/V	0.5208	ambiguous	0.4759	ambiguous	-0.48	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	I
P/W	0.9348	likely_pathogenic	0.9081	pathogenic	-0.887	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	I
P/Y	0.8602	likely_pathogenic	0.8132	pathogenic	-0.613	Destabilizing	1.0	D	0.698	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.