TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29598	89017;89018;89019	chr2:178554555;178554554;178554553	chr2:179419282;179419281;179419280
N2AB	27957	84094;84095;84096	chr2:178554555;178554554;178554553	chr2:179419282;179419281;179419280
N2A	27030	81313;81314;81315	chr2:178554555;178554554;178554553	chr2:179419282;179419281;179419280
N2B	20533	61822;61823;61824	chr2:178554555;178554554;178554553	chr2:179419282;179419281;179419280
Novex-1	20658	62197;62198;62199	chr2:178554555;178554554;178554553	chr2:179419282;179419281;179419280
Novex-2	20725	62398;62399;62400	chr2:178554555;178554554;178554553	chr2:179419282;179419281;179419280
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: Fn3-103
• Domain position: 66
• Structural Position: 97
• Q(SASA): 0.0986
• 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
I/S	None	None	0.301	N	0.708	0.406	0.742855381746	gnomAD-4.0.0	1.59112E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85788E-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
I/A	0.8854	likely_pathogenic	0.901	pathogenic	-2.435	Highly Destabilizing	0.055	N	0.637	neutral	None	None	None	None	N
I/C	0.8995	likely_pathogenic	0.9144	pathogenic	-1.678	Destabilizing	0.859	D	0.755	deleterious	None	None	None	None	N
I/D	0.9963	likely_pathogenic	0.9961	pathogenic	-2.149	Highly Destabilizing	0.859	D	0.796	deleterious	None	None	None	None	N
I/E	0.9907	likely_pathogenic	0.9908	pathogenic	-2.034	Highly Destabilizing	0.667	D	0.786	deleterious	None	None	None	None	N
I/F	0.5906	likely_pathogenic	0.6268	pathogenic	-1.591	Destabilizing	0.096	N	0.649	neutral	N	0.463108309	None	None	N
I/G	0.9798	likely_pathogenic	0.9825	pathogenic	-2.897	Highly Destabilizing	0.364	N	0.77	deleterious	None	None	None	None	N
I/H	0.9803	likely_pathogenic	0.9818	pathogenic	-2.095	Highly Destabilizing	0.958	D	0.813	deleterious	None	None	None	None	N
I/K	0.983	likely_pathogenic	0.9826	pathogenic	-1.829	Destabilizing	0.364	N	0.768	deleterious	None	None	None	None	N
I/L	0.0867	likely_benign	0.1193	benign	-1.156	Destabilizing	None	N	0.313	neutral	N	0.213346632	None	None	N
I/M	0.1696	likely_benign	0.194	benign	-0.94	Destabilizing	0.427	N	0.645	neutral	N	0.408697821	None	None	N
I/N	0.929	likely_pathogenic	0.9224	pathogenic	-1.851	Destabilizing	0.822	D	0.807	deleterious	N	0.482387503	None	None	N
I/P	0.9812	likely_pathogenic	0.9839	pathogenic	-1.557	Destabilizing	0.859	D	0.802	deleterious	None	None	None	None	N
I/Q	0.9747	likely_pathogenic	0.9754	pathogenic	-1.9	Destabilizing	0.859	D	0.807	deleterious	None	None	None	None	N
I/R	0.9757	likely_pathogenic	0.9763	pathogenic	-1.283	Destabilizing	0.667	D	0.799	deleterious	None	None	None	None	N
I/S	0.9456	likely_pathogenic	0.9454	pathogenic	-2.587	Highly Destabilizing	0.301	N	0.708	prob.delet.	N	0.482214144	None	None	N
I/T	0.8738	likely_pathogenic	0.8859	pathogenic	-2.335	Highly Destabilizing	0.175	N	0.682	prob.neutral	N	0.452584671	None	None	N
I/V	0.125	likely_benign	0.1394	benign	-1.557	Destabilizing	None	N	0.29	neutral	N	0.386706395	None	None	N
I/W	0.9825	likely_pathogenic	0.9856	pathogenic	-1.787	Destabilizing	0.958	D	0.807	deleterious	None	None	None	None	N
I/Y	0.9335	likely_pathogenic	0.9352	pathogenic	-1.565	Destabilizing	0.667	D	0.733	prob.delet.	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.