TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2544	7855;7856;7857	chr2:178773334;178773333;178773332	chr2:179638061;179638060;179638059
N2AB	2544	7855;7856;7857	chr2:178773334;178773333;178773332	chr2:179638061;179638060;179638059
N2A	2544	7855;7856;7857	chr2:178773334;178773333;178773332	chr2:179638061;179638060;179638059
N2B	2498	7717;7718;7719	chr2:178773334;178773333;178773332	chr2:179638061;179638060;179638059
Novex-1	2498	7717;7718;7719	chr2:178773334;178773333;178773332	chr2:179638061;179638060;179638059
Novex-2	2498	7717;7718;7719	chr2:178773334;178773333;178773332	chr2:179638061;179638060;179638059
Novex-3	2544	7855;7856;7857	chr2:178773334;178773333;178773332	chr2:179638061;179638060;179638059

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-15
• Domain position: 12
• Structural Position: 16
• Q(SASA): 0.1449
• 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
C/Y	rs1271799350	None	1.0	D	0.727	0.624	0.808542943238	gnomAD-4.0.0	1.59084E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85672E-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
C/A	0.3856	ambiguous	0.3862	ambiguous	-1.213	Destabilizing	0.998	D	0.499	neutral	None	None	None	None	N
C/D	0.9088	likely_pathogenic	0.8878	pathogenic	0.03	Stabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
C/E	0.9443	likely_pathogenic	0.9329	pathogenic	0.065	Stabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
C/F	0.5028	ambiguous	0.4704	ambiguous	-0.861	Destabilizing	1.0	D	0.732	prob.delet.	D	0.581506638	None	None	N
C/G	0.2385	likely_benign	0.2247	benign	-1.456	Destabilizing	1.0	D	0.761	deleterious	D	0.540095777	None	None	N
C/H	0.8368	likely_pathogenic	0.8108	pathogenic	-1.567	Destabilizing	1.0	D	0.711	prob.delet.	None	None	None	None	N
C/I	0.6508	likely_pathogenic	0.6349	pathogenic	-0.627	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
C/K	0.9358	likely_pathogenic	0.9235	pathogenic	-0.487	Destabilizing	1.0	D	0.742	deleterious	None	None	None	None	N
C/L	0.7029	likely_pathogenic	0.6796	pathogenic	-0.627	Destabilizing	0.999	D	0.599	neutral	None	None	None	None	N
C/M	0.8004	likely_pathogenic	0.7923	pathogenic	0.041	Stabilizing	1.0	D	0.698	prob.neutral	None	None	None	None	N
C/N	0.7986	likely_pathogenic	0.7715	pathogenic	-0.276	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
C/P	0.9888	likely_pathogenic	0.9851	pathogenic	-0.796	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	N
C/Q	0.8519	likely_pathogenic	0.8414	pathogenic	-0.333	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	N
C/R	0.7244	likely_pathogenic	0.6893	pathogenic	-0.286	Destabilizing	1.0	D	0.747	deleterious	D	0.581653883	None	None	N
C/S	0.3501	ambiguous	0.3457	ambiguous	-0.789	Destabilizing	1.0	D	0.751	deleterious	N	0.501156472	None	None	N
C/T	0.535	ambiguous	0.5247	ambiguous	-0.592	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	N
C/V	0.4811	ambiguous	0.4753	ambiguous	-0.796	Destabilizing	0.999	D	0.686	prob.neutral	None	None	None	None	N
C/W	0.8732	likely_pathogenic	0.8569	pathogenic	-0.822	Destabilizing	1.0	D	0.661	neutral	D	0.583316423	None	None	N
C/Y	0.6772	likely_pathogenic	0.6361	pathogenic	-0.757	Destabilizing	1.0	D	0.727	prob.delet.	D	0.581653883	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.