TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	23444	70555;70556;70557	chr2:178575802;178575801;178575800	chr2:179440529;179440528;179440527
N2AB	21803	65632;65633;65634	chr2:178575802;178575801;178575800	chr2:179440529;179440528;179440527
N2A	20876	62851;62852;62853	chr2:178575802;178575801;178575800	chr2:179440529;179440528;179440527
N2B	14379	43360;43361;43362	chr2:178575802;178575801;178575800	chr2:179440529;179440528;179440527
Novex-1	14504	43735;43736;43737	chr2:178575802;178575801;178575800	chr2:179440529;179440528;179440527
Novex-2	14571	43936;43937;43938	chr2:178575802;178575801;178575800	chr2:179440529;179440528;179440527
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Fn3-58
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.3583
• 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
P/R	rs1325284144	None	0.997	N	0.869	0.398	0.446813524615	gnomAD-3.1.2	6.58E-06	None	None	None	None	N	None	0	0	0	0	0	None	0	0	1.47E-05	0	0
P/R	rs1325284144	None	0.997	N	0.869	0.398	0.446813524615	gnomAD-4.0.0	5.12919E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.58414E-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
P/A	0.1093	likely_benign	0.1155	benign	-1.782	Destabilizing	0.117	N	0.33	neutral	N	0.392549358	None	None	N
P/C	0.5105	ambiguous	0.5189	ambiguous	-1.181	Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
P/D	0.9384	likely_pathogenic	0.955	pathogenic	-1.711	Destabilizing	0.998	D	0.802	deleterious	None	None	None	None	N
P/E	0.8015	likely_pathogenic	0.8357	pathogenic	-1.622	Destabilizing	0.995	D	0.772	deleterious	None	None	None	None	N
P/F	0.7037	likely_pathogenic	0.7262	pathogenic	-1.216	Destabilizing	1.0	D	0.852	deleterious	None	None	None	None	N
P/G	0.6116	likely_pathogenic	0.6584	pathogenic	-2.195	Highly Destabilizing	0.966	D	0.701	prob.neutral	None	None	None	None	N
P/H	0.6056	likely_pathogenic	0.6503	pathogenic	-1.694	Destabilizing	1.0	D	0.827	deleterious	N	0.475074741	None	None	N
P/I	0.2878	likely_benign	0.2801	benign	-0.701	Destabilizing	0.995	D	0.863	deleterious	None	None	None	None	N
P/K	0.805	likely_pathogenic	0.8428	pathogenic	-1.525	Destabilizing	0.995	D	0.778	deleterious	None	None	None	None	N
P/L	0.1909	likely_benign	0.1943	benign	-0.701	Destabilizing	0.993	D	0.797	deleterious	N	0.396611171	None	None	N
P/M	0.4122	ambiguous	0.446	ambiguous	-0.548	Destabilizing	1.0	D	0.834	deleterious	None	None	None	None	N
P/N	0.7934	likely_pathogenic	0.8391	pathogenic	-1.458	Destabilizing	0.998	D	0.871	deleterious	None	None	None	None	N
P/Q	0.5652	likely_pathogenic	0.6199	pathogenic	-1.495	Destabilizing	0.998	D	0.833	deleterious	None	None	None	None	N
P/R	0.7124	likely_pathogenic	0.7596	pathogenic	-1.104	Destabilizing	0.997	D	0.869	deleterious	N	0.511899546	None	None	N
P/S	0.352	ambiguous	0.4018	ambiguous	-2.039	Highly Destabilizing	0.955	D	0.699	prob.neutral	N	0.474381308	None	None	N
P/T	0.1842	likely_benign	0.2123	benign	-1.817	Destabilizing	0.993	D	0.751	deleterious	N	0.434150839	None	None	N
P/V	0.1876	likely_benign	0.1799	benign	-1.029	Destabilizing	0.99	D	0.772	deleterious	None	None	None	None	N
P/W	0.8961	likely_pathogenic	0.9127	pathogenic	-1.496	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
P/Y	0.7193	likely_pathogenic	0.7493	pathogenic	-1.182	Destabilizing	1.0	D	0.847	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.