TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	32347	97264;97265;97266	chr2:178542815;178542814;178542813	chr2:179407542;179407541;179407540
N2AB	30706	92341;92342;92343	chr2:178542815;178542814;178542813	chr2:179407542;179407541;179407540
N2A	29779	89560;89561;89562	chr2:178542815;178542814;178542813	chr2:179407542;179407541;179407540
N2B	23282	70069;70070;70071	chr2:178542815;178542814;178542813	chr2:179407542;179407541;179407540
Novex-1	23407	70444;70445;70446	chr2:178542815;178542814;178542813	chr2:179407542;179407541;179407540
Novex-2	23474	70645;70646;70647	chr2:178542815;178542814;178542813	chr2:179407542;179407541;179407540
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTG
• RefSeq wild type template codon: GAC
• Domain: Ig-154
• Domain position: 41
• Structural Position: 58
• Q(SASA): 0.1965
• 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
L/V	None	None	0.17	N	0.377	0.162	0.381580015636	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
L/A	0.7906	likely_pathogenic	0.7121	pathogenic	-1.926	Destabilizing	0.953	D	0.495	neutral	None	None	None	None	N
L/C	0.8517	likely_pathogenic	0.7778	pathogenic	-1.203	Destabilizing	0.999	D	0.659	neutral	None	None	None	None	N
L/D	0.9875	likely_pathogenic	0.9803	pathogenic	-1.674	Destabilizing	0.998	D	0.781	deleterious	None	None	None	None	N
L/E	0.9186	likely_pathogenic	0.8817	pathogenic	-1.459	Destabilizing	0.998	D	0.765	deleterious	None	None	None	None	N
L/F	0.4334	ambiguous	0.325	benign	-1.122	Destabilizing	0.986	D	0.573	neutral	None	None	None	None	N
L/G	0.9425	likely_pathogenic	0.9071	pathogenic	-2.403	Highly Destabilizing	0.993	D	0.747	deleterious	None	None	None	None	N
L/H	0.8673	likely_pathogenic	0.7938	pathogenic	-1.598	Destabilizing	0.999	D	0.767	deleterious	None	None	None	None	N
L/I	0.1076	likely_benign	0.1013	benign	-0.565	Destabilizing	0.06	N	0.398	neutral	None	None	None	None	N
L/K	0.8537	likely_pathogenic	0.8054	pathogenic	-1.288	Destabilizing	0.993	D	0.712	prob.delet.	None	None	None	None	N
L/M	0.2014	likely_benign	0.1637	benign	-0.587	Destabilizing	0.76	D	0.455	neutral	N	0.512544267	None	None	N
L/N	0.9314	likely_pathogenic	0.9056	pathogenic	-1.653	Destabilizing	0.998	D	0.782	deleterious	None	None	None	None	N
L/P	0.848	likely_pathogenic	0.7854	pathogenic	-0.998	Destabilizing	0.997	D	0.781	deleterious	D	0.536270836	None	None	N
L/Q	0.7551	likely_pathogenic	0.651	pathogenic	-1.48	Destabilizing	0.991	D	0.744	deleterious	D	0.536524326	None	None	N
L/R	0.8221	likely_pathogenic	0.7404	pathogenic	-1.142	Destabilizing	0.991	D	0.744	deleterious	D	0.536270836	None	None	N
L/S	0.9298	likely_pathogenic	0.8868	pathogenic	-2.349	Highly Destabilizing	0.993	D	0.69	prob.neutral	None	None	None	None	N
L/T	0.7982	likely_pathogenic	0.7201	pathogenic	-1.978	Destabilizing	0.986	D	0.606	neutral	None	None	None	None	N
L/V	0.1578	likely_benign	0.1375	benign	-0.998	Destabilizing	0.17	N	0.377	neutral	N	0.517055516	None	None	N
L/W	0.7309	likely_pathogenic	0.5978	pathogenic	-1.336	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
L/Y	0.8023	likely_pathogenic	0.7037	pathogenic	-1.029	Destabilizing	0.998	D	0.697	prob.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.