TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21569	64930;64931;64932	chr2:178584936;178584935;178584934	chr2:179449663;179449662;179449661
N2AB	19928	60007;60008;60009	chr2:178584936;178584935;178584934	chr2:179449663;179449662;179449661
N2A	19001	57226;57227;57228	chr2:178584936;178584935;178584934	chr2:179449663;179449662;179449661
N2B	12504	37735;37736;37737	chr2:178584936;178584935;178584934	chr2:179449663;179449662;179449661
Novex-1	12629	38110;38111;38112	chr2:178584936;178584935;178584934	chr2:179449663;179449662;179449661
Novex-2	12696	38311;38312;38313	chr2:178584936;178584935;178584934	chr2:179449663;179449662;179449661
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Fn3-44
• Domain position: 11
• Structural Position: 12
• Q(SASA): 0.8027
• 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
I/V	None	None	0.4	N	0.235	0.071	0.446111551642	gnomAD-4.0.0	1.59246E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43336E-05	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
I/A	0.7442	likely_pathogenic	0.7405	pathogenic	-2.302	Highly Destabilizing	0.985	D	0.58	neutral	None	None	None	None	I
I/C	0.8338	likely_pathogenic	0.8113	pathogenic	-1.773	Destabilizing	1.0	D	0.666	neutral	None	None	None	None	I
I/D	0.9727	likely_pathogenic	0.9773	pathogenic	-1.597	Destabilizing	0.999	D	0.734	prob.delet.	None	None	None	None	I
I/E	0.9516	likely_pathogenic	0.9586	pathogenic	-1.462	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	I
I/F	0.2379	likely_benign	0.2305	benign	-1.495	Destabilizing	0.265	N	0.401	neutral	N	0.452197882	None	None	I
I/G	0.9472	likely_pathogenic	0.9462	pathogenic	-2.778	Highly Destabilizing	0.999	D	0.709	prob.delet.	None	None	None	None	I
I/H	0.8993	likely_pathogenic	0.9115	pathogenic	-2.03	Highly Destabilizing	1.0	D	0.71	prob.delet.	None	None	None	None	I
I/K	0.8773	likely_pathogenic	0.8999	pathogenic	-1.588	Destabilizing	0.999	D	0.737	prob.delet.	None	None	None	None	I
I/L	0.1896	likely_benign	0.1748	benign	-0.985	Destabilizing	0.817	D	0.452	neutral	N	0.468879488	None	None	I
I/M	0.1981	likely_benign	0.1988	benign	-0.945	Destabilizing	0.997	D	0.599	neutral	N	0.485829416	None	None	I
I/N	0.7846	likely_pathogenic	0.7983	pathogenic	-1.618	Destabilizing	0.999	D	0.734	prob.delet.	N	0.50946708	None	None	I
I/P	0.9384	likely_pathogenic	0.9423	pathogenic	-1.398	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	I
I/Q	0.8979	likely_pathogenic	0.9121	pathogenic	-1.604	Destabilizing	0.999	D	0.736	prob.delet.	None	None	None	None	I
I/R	0.8145	likely_pathogenic	0.8441	pathogenic	-1.21	Destabilizing	0.999	D	0.739	prob.delet.	None	None	None	None	I
I/S	0.7792	likely_pathogenic	0.7921	pathogenic	-2.447	Highly Destabilizing	0.997	D	0.676	prob.neutral	N	0.483854407	None	None	I
I/T	0.6672	likely_pathogenic	0.687	pathogenic	-2.16	Highly Destabilizing	0.98	D	0.609	neutral	N	0.47949954	None	None	I
I/V	0.105	likely_benign	0.099	benign	-1.398	Destabilizing	0.4	N	0.235	neutral	N	0.457774273	None	None	I
I/W	0.9296	likely_pathogenic	0.9298	pathogenic	-1.639	Destabilizing	1.0	D	0.732	prob.delet.	None	None	None	None	I
I/Y	0.7658	likely_pathogenic	0.7673	pathogenic	-1.402	Destabilizing	0.991	D	0.653	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.