TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20732	62419;62420;62421	chr2:178589531;178589530;178589529	chr2:179454258;179454257;179454256
N2AB	19091	57496;57497;57498	chr2:178589531;178589530;178589529	chr2:179454258;179454257;179454256
N2A	18164	54715;54716;54717	chr2:178589531;178589530;178589529	chr2:179454258;179454257;179454256
N2B	11667	35224;35225;35226	chr2:178589531;178589530;178589529	chr2:179454258;179454257;179454256
Novex-1	11792	35599;35600;35601	chr2:178589531;178589530;178589529	chr2:179454258;179454257;179454256
Novex-2	11859	35800;35801;35802	chr2:178589531;178589530;178589529	chr2:179454258;179454257;179454256
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Fn3-38
• Domain position: 65
• Structural Position: 96
• Q(SASA): 0.8485
• 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
R/S	None	None	0.012	N	0.279	0.062	0.158396225186	gnomAD-4.0.0	6.36819E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.14362E-05	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
R/A	0.3542	ambiguous	0.4155	ambiguous	-0.047	Destabilizing	0.007	N	0.262	neutral	None	None	None	None	N
R/C	0.2329	likely_benign	0.3362	benign	-0.163	Destabilizing	0.864	D	0.355	neutral	None	None	None	None	N
R/D	0.5051	ambiguous	0.5711	pathogenic	-0.264	Destabilizing	0.031	N	0.31	neutral	None	None	None	None	N
R/E	0.3299	likely_benign	0.4358	ambiguous	-0.227	Destabilizing	0.007	N	0.225	neutral	None	None	None	None	N
R/F	0.6393	likely_pathogenic	0.7686	pathogenic	-0.353	Destabilizing	0.628	D	0.383	neutral	None	None	None	None	N
R/G	0.1831	likely_benign	0.2197	benign	-0.197	Destabilizing	0.024	N	0.275	neutral	N	0.396664312	None	None	N
R/H	0.1021	likely_benign	0.1258	benign	-0.67	Destabilizing	0.356	N	0.369	neutral	None	None	None	None	N
R/I	0.451	ambiguous	0.5581	ambiguous	0.302	Stabilizing	0.106	N	0.431	neutral	N	0.467659028	None	None	N
R/K	0.0562	likely_benign	0.0705	benign	-0.141	Destabilizing	None	N	0.202	neutral	N	0.41146598	None	None	N
R/L	0.3184	likely_benign	0.4295	ambiguous	0.302	Stabilizing	0.031	N	0.275	neutral	None	None	None	None	N
R/M	0.3016	likely_benign	0.4193	ambiguous	-0.006	Destabilizing	0.628	D	0.383	neutral	None	None	None	None	N
R/N	0.3648	ambiguous	0.4267	ambiguous	0.084	Stabilizing	0.031	N	0.283	neutral	None	None	None	None	N
R/P	0.8346	likely_pathogenic	0.8719	pathogenic	0.204	Stabilizing	0.136	N	0.385	neutral	None	None	None	None	N
R/Q	0.105	likely_benign	0.132	benign	-0.033	Destabilizing	0.016	N	0.3	neutral	None	None	None	None	N
R/S	0.3654	ambiguous	0.4229	ambiguous	-0.188	Destabilizing	0.012	N	0.279	neutral	N	0.439113941	None	None	N
R/T	0.2488	likely_benign	0.3058	benign	-0.042	Destabilizing	0.024	N	0.299	neutral	N	0.48477166	None	None	N
R/V	0.4743	ambiguous	0.5737	pathogenic	0.204	Stabilizing	0.072	N	0.365	neutral	None	None	None	None	N
R/W	0.3237	likely_benign	0.4878	ambiguous	-0.468	Destabilizing	0.864	D	0.35	neutral	None	None	None	None	N
R/Y	0.4568	ambiguous	0.6261	pathogenic	-0.068	Destabilizing	0.356	N	0.4	neutral	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.