TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14757	44494;44495;44496	chr2:178630253;178630252;178630251	chr2:179494980;179494979;179494978
N2AB	13116	39571;39572;39573	chr2:178630253;178630252;178630251	chr2:179494980;179494979;179494978
N2A	12189	36790;36791;36792	chr2:178630253;178630252;178630251	chr2:179494980;179494979;179494978
N2B	5692	17299;17300;17301	chr2:178630253;178630252;178630251	chr2:179494980;179494979;179494978
Novex-1	5817	17674;17675;17676	chr2:178630253;178630252;178630251	chr2:179494980;179494979;179494978
Novex-2	5884	17875;17876;17877	chr2:178630253;178630252;178630251	chr2:179494980;179494979;179494978
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-98
• Domain position: 83
• Structural Position: 174
• Q(SASA): 0.1163
• 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/F	None	None	0.999	D	0.831	0.393	0.515603885326	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	0.9814	likely_pathogenic	0.9831	pathogenic	-2.954	Highly Destabilizing	0.997	D	0.677	prob.neutral	None	None	None	None	N
L/C	0.9549	likely_pathogenic	0.9554	pathogenic	-2.188	Highly Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
L/D	0.9997	likely_pathogenic	0.9998	pathogenic	-3.468	Highly Destabilizing	1.0	D	0.902	deleterious	None	None	None	None	N
L/E	0.9969	likely_pathogenic	0.998	pathogenic	-3.191	Highly Destabilizing	1.0	D	0.888	deleterious	None	None	None	None	N
L/F	0.7382	likely_pathogenic	0.8255	pathogenic	-1.803	Destabilizing	0.999	D	0.831	deleterious	D	0.641536656	None	None	N
L/G	0.9947	likely_pathogenic	0.9957	pathogenic	-3.55	Highly Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/H	0.9925	likely_pathogenic	0.9947	pathogenic	-3.031	Highly Destabilizing	1.0	D	0.908	deleterious	D	0.644762009	None	None	N
L/I	0.2923	likely_benign	0.3519	ambiguous	-1.194	Destabilizing	0.779	D	0.277	neutral	D	0.63756027	None	None	N
L/K	0.9913	likely_pathogenic	0.9946	pathogenic	-2.485	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/M	0.5162	ambiguous	0.5873	pathogenic	-1.114	Destabilizing	0.999	D	0.818	deleterious	None	None	None	None	N
L/N	0.9978	likely_pathogenic	0.9985	pathogenic	-3.006	Highly Destabilizing	1.0	D	0.907	deleterious	None	None	None	None	N
L/P	0.9974	likely_pathogenic	0.9987	pathogenic	-1.767	Destabilizing	1.0	D	0.903	deleterious	D	0.644762009	None	None	N
L/Q	0.9854	likely_pathogenic	0.991	pathogenic	-2.774	Highly Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
L/R	0.9807	likely_pathogenic	0.9873	pathogenic	-2.219	Highly Destabilizing	1.0	D	0.919	deleterious	D	0.643160475	None	None	N
L/S	0.9967	likely_pathogenic	0.9975	pathogenic	-3.683	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
L/T	0.9866	likely_pathogenic	0.9885	pathogenic	-3.25	Highly Destabilizing	0.999	D	0.793	deleterious	None	None	None	None	N
L/V	0.4157	ambiguous	0.4504	ambiguous	-1.767	Destabilizing	0.959	D	0.584	neutral	D	0.589561095	None	None	N
L/W	0.977	likely_pathogenic	0.9847	pathogenic	-2.255	Highly Destabilizing	1.0	D	0.897	deleterious	None	None	None	None	N
L/Y	0.9817	likely_pathogenic	0.9875	pathogenic	-2.0	Highly Destabilizing	1.0	D	0.871	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.