TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	2337	7234;7235;7236	chr2:178774255;178774254;178774253	chr2:179638982;179638981;179638980
N2AB	2337	7234;7235;7236	chr2:178774255;178774254;178774253	chr2:179638982;179638981;179638980
N2A	2337	7234;7235;7236	chr2:178774255;178774254;178774253	chr2:179638982;179638981;179638980
N2B	2291	7096;7097;7098	chr2:178774255;178774254;178774253	chr2:179638982;179638981;179638980
Novex-1	2291	7096;7097;7098	chr2:178774255;178774254;178774253	chr2:179638982;179638981;179638980
Novex-2	2291	7096;7097;7098	chr2:178774255;178774254;178774253	chr2:179638982;179638981;179638980
Novex-3	2337	7234;7235;7236	chr2:178774255;178774254;178774253	chr2:179638982;179638981;179638980

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-12
• Domain position: 71
• Structural Position: 155
• Q(SASA): 0.1096
• 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
S/G	None	None	0.815	N	0.615	0.205	0.198526703765	gnomAD-4.0.0	1.59057E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-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
S/A	0.0938	likely_benign	0.0958	benign	-0.878	Destabilizing	0.206	N	0.423	neutral	None	None	None	None	N
S/C	0.1001	likely_benign	0.1015	benign	-0.24	Destabilizing	0.015	N	0.529	neutral	N	0.468642816	None	None	N
S/D	0.7123	likely_pathogenic	0.7012	pathogenic	-1.66	Destabilizing	0.854	D	0.643	neutral	None	None	None	None	N
S/E	0.6893	likely_pathogenic	0.6815	pathogenic	-1.359	Destabilizing	0.854	D	0.647	neutral	None	None	None	None	N
S/F	0.2743	likely_benign	0.2966	benign	-0.574	Destabilizing	0.91	D	0.745	deleterious	None	None	None	None	N
S/G	0.1373	likely_benign	0.1418	benign	-1.306	Destabilizing	0.815	D	0.615	neutral	N	0.506647237	None	None	N
S/H	0.3795	ambiguous	0.382	ambiguous	-1.347	Destabilizing	0.996	D	0.714	prob.delet.	None	None	None	None	N
S/I	0.209	likely_benign	0.2227	benign	0.271	Stabilizing	0.028	N	0.613	neutral	N	0.448065193	None	None	N
S/K	0.7461	likely_pathogenic	0.7278	pathogenic	0.445	Stabilizing	0.742	D	0.649	neutral	None	None	None	None	N
S/L	0.1636	likely_benign	0.1742	benign	0.271	Stabilizing	0.373	N	0.681	prob.neutral	None	None	None	None	N
S/M	0.2597	likely_benign	0.2847	benign	-0.181	Destabilizing	0.953	D	0.729	prob.delet.	None	None	None	None	N
S/N	0.2598	likely_benign	0.254	benign	-0.549	Destabilizing	0.815	D	0.641	neutral	N	0.467790772	None	None	N
S/P	0.983	likely_pathogenic	0.9817	pathogenic	-0.084	Destabilizing	0.984	D	0.765	deleterious	None	None	None	None	N
S/Q	0.5658	likely_pathogenic	0.5659	pathogenic	-0.073	Destabilizing	0.984	D	0.68	prob.neutral	None	None	None	None	N
S/R	0.5915	likely_pathogenic	0.5713	pathogenic	-0.26	Destabilizing	0.939	D	0.76	deleterious	N	0.445800494	None	None	N
S/T	0.0749	likely_benign	0.077	benign	-0.112	Destabilizing	0.004	N	0.213	neutral	N	0.384117835	None	None	N
S/V	0.2082	likely_benign	0.2227	benign	-0.084	Destabilizing	0.373	N	0.685	prob.neutral	None	None	None	None	N
S/W	0.4747	ambiguous	0.4991	ambiguous	-0.93	Destabilizing	0.996	D	0.761	deleterious	None	None	None	None	N
S/Y	0.2374	likely_benign	0.2501	benign	-0.437	Destabilizing	0.984	D	0.737	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.