TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20932	63019;63020;63021	chr2:178588931;178588930;178588929	chr2:179453658;179453657;179453656
N2AB	19291	58096;58097;58098	chr2:178588931;178588930;178588929	chr2:179453658;179453657;179453656
N2A	18364	55315;55316;55317	chr2:178588931;178588930;178588929	chr2:179453658;179453657;179453656
N2B	11867	35824;35825;35826	chr2:178588931;178588930;178588929	chr2:179453658;179453657;179453656
Novex-1	11992	36199;36200;36201	chr2:178588931;178588930;178588929	chr2:179453658;179453657;179453656
Novex-2	12059	36400;36401;36402	chr2:178588931;178588930;178588929	chr2:179453658;179453657;179453656
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-39
• Domain position: 69
• Structural Position: 102
• Q(SASA): 0.388
• 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
N/Y	None	None	1.0	N	0.663	0.536	0.497547018531	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
N/A	0.7412	likely_pathogenic	0.7833	pathogenic	-0.955	Destabilizing	1.0	D	0.647	neutral	None	None	None	None	N
N/C	0.4988	ambiguous	0.5095	ambiguous	-0.035	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	N
N/D	0.7339	likely_pathogenic	0.8436	pathogenic	-0.515	Destabilizing	0.999	D	0.539	neutral	N	0.477116003	None	None	N
N/E	0.9256	likely_pathogenic	0.9523	pathogenic	-0.382	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
N/F	0.9175	likely_pathogenic	0.9259	pathogenic	-0.554	Destabilizing	1.0	D	0.682	prob.neutral	None	None	None	None	N
N/G	0.6867	likely_pathogenic	0.7485	pathogenic	-1.326	Destabilizing	0.999	D	0.457	neutral	None	None	None	None	N
N/H	0.3266	likely_benign	0.3608	ambiguous	-0.894	Destabilizing	1.0	D	0.689	prob.neutral	N	0.499759755	None	None	N
N/I	0.7869	likely_pathogenic	0.8211	pathogenic	0.01	Stabilizing	1.0	D	0.667	neutral	N	0.474647241	None	None	N
N/K	0.9047	likely_pathogenic	0.9413	pathogenic	-0.261	Destabilizing	1.0	D	0.667	neutral	N	0.469455491	None	None	N
N/L	0.7229	likely_pathogenic	0.7906	pathogenic	0.01	Stabilizing	1.0	D	0.672	neutral	None	None	None	None	N
N/M	0.7736	likely_pathogenic	0.793	pathogenic	0.362	Stabilizing	1.0	D	0.631	neutral	None	None	None	None	N
N/P	0.9826	likely_pathogenic	0.986	pathogenic	-0.282	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
N/Q	0.8182	likely_pathogenic	0.8494	pathogenic	-0.784	Destabilizing	1.0	D	0.675	prob.neutral	None	None	None	None	N
N/R	0.868	likely_pathogenic	0.9076	pathogenic	-0.329	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
N/S	0.2117	likely_benign	0.2405	benign	-0.979	Destabilizing	0.999	D	0.478	neutral	N	0.497852813	None	None	N
N/T	0.5901	likely_pathogenic	0.6098	pathogenic	-0.642	Destabilizing	0.999	D	0.634	neutral	N	0.428832658	None	None	N
N/V	0.7508	likely_pathogenic	0.778	pathogenic	-0.282	Destabilizing	1.0	D	0.653	neutral	None	None	None	None	N
N/W	0.9633	likely_pathogenic	0.9659	pathogenic	-0.295	Destabilizing	1.0	D	0.65	neutral	None	None	None	None	N
N/Y	0.561	ambiguous	0.6252	pathogenic	-0.088	Destabilizing	1.0	D	0.663	neutral	N	0.507083542	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.