TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8666	26221;26222;26223	chr2:178715190;178715189;178715188	chr2:179579917;179579916;179579915
N2AB	8349	25270;25271;25272	chr2:178715190;178715189;178715188	chr2:179579917;179579916;179579915
N2A	7422	22489;22490;22491	chr2:178715190;178715189;178715188	chr2:179579917;179579916;179579915
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-72
• Domain position: 24
• Structural Position: 35
• Q(SASA): 0.0937
• 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
L/F	None	None	0.998	D	0.765	0.299	0.515603885326	gnomAD-4.0.0	2.73703E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79908E-06	2.31906E-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
L/A	0.8723	likely_pathogenic	0.855	pathogenic	-2.509	Highly Destabilizing	0.998	D	0.716	prob.delet.	None	None	None	None	N
L/C	0.8704	likely_pathogenic	0.8619	pathogenic	-1.461	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
L/D	0.9977	likely_pathogenic	0.9969	pathogenic	-2.786	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
L/E	0.9853	likely_pathogenic	0.9791	pathogenic	-2.499	Highly Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
L/F	0.4544	ambiguous	0.4123	ambiguous	-1.425	Destabilizing	0.998	D	0.765	deleterious	D	0.534616982	None	None	N
L/G	0.9719	likely_pathogenic	0.9655	pathogenic	-3.094	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
L/H	0.9601	likely_pathogenic	0.9461	pathogenic	-2.66	Highly Destabilizing	1.0	D	0.817	deleterious	N	0.494139481	None	None	N
L/I	0.1058	likely_benign	0.1025	benign	-0.777	Destabilizing	0.142	N	0.33	neutral	N	0.446165704	None	None	N
L/K	0.9753	likely_pathogenic	0.9651	pathogenic	-1.667	Destabilizing	0.991	D	0.807	deleterious	None	None	None	None	N
L/M	0.2315	likely_benign	0.2248	benign	-0.761	Destabilizing	0.932	D	0.548	neutral	None	None	None	None	N
L/N	0.9789	likely_pathogenic	0.973	pathogenic	-2.172	Highly Destabilizing	1.0	D	0.827	deleterious	None	None	None	None	N
L/P	0.9798	likely_pathogenic	0.9748	pathogenic	-1.341	Destabilizing	1.0	D	0.821	deleterious	N	0.486287104	None	None	N
L/Q	0.9417	likely_pathogenic	0.9236	pathogenic	-1.905	Destabilizing	0.999	D	0.786	deleterious	None	None	None	None	N
L/R	0.954	likely_pathogenic	0.9369	pathogenic	-1.639	Destabilizing	0.999	D	0.783	deleterious	N	0.500722846	None	None	N
L/S	0.9651	likely_pathogenic	0.9565	pathogenic	-2.831	Highly Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	N
L/T	0.8741	likely_pathogenic	0.8499	pathogenic	-2.391	Highly Destabilizing	0.998	D	0.79	deleterious	None	None	None	None	N
L/V	0.1567	likely_benign	0.1494	benign	-1.341	Destabilizing	0.179	N	0.336	neutral	N	0.386706395	None	None	N
L/W	0.8685	likely_pathogenic	0.8353	pathogenic	-1.841	Destabilizing	1.0	D	0.786	deleterious	None	None	None	None	N
L/Y	0.8792	likely_pathogenic	0.8492	pathogenic	-1.56	Destabilizing	0.998	D	0.769	deleterious	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.