TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	20789	62590;62591;62592	chr2:178589360;178589359;178589358	chr2:179454087;179454086;179454085
N2AB	19148	57667;57668;57669	chr2:178589360;178589359;178589358	chr2:179454087;179454086;179454085
N2A	18221	54886;54887;54888	chr2:178589360;178589359;178589358	chr2:179454087;179454086;179454085
N2B	11724	35395;35396;35397	chr2:178589360;178589359;178589358	chr2:179454087;179454086;179454085
Novex-1	11849	35770;35771;35772	chr2:178589360;178589359;178589358	chr2:179454087;179454086;179454085
Novex-2	11916	35971;35972;35973	chr2:178589360;178589359;178589358	chr2:179454087;179454086;179454085
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTT
• RefSeq wild type template codon: GAA
• Domain: Ig-122
• Domain position: 21
• Structural Position: 30
• Q(SASA): 0.1716
• 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/P	rs750434015	-1.387	0.028	D	0.686	0.715	None	gnomAD-2.1.1	1.07E-05	None	None	None	None	N	None	1.24069E-04	0	None	0	0	None	0	None	0	0	0
L/P	rs750434015	-1.387	0.028	D	0.686	0.715	None	gnomAD-3.1.2	2.63E-05	None	None	None	None	N	None	9.66E-05	0	0	0	0	None	0	0	0	0	0
L/P	rs750434015	-1.387	0.028	D	0.686	0.715	None	gnomAD-4.0.0	3.71921E-06	None	None	None	None	N	None	8.01368E-05	0	None	0	0	None	0	0	0	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	0.9135	likely_pathogenic	0.9304	pathogenic	-2.38	Highly Destabilizing	0.842	D	0.701	prob.neutral	None	None	None	None	N
L/C	0.9271	likely_pathogenic	0.9403	pathogenic	-1.606	Destabilizing	0.998	D	0.783	deleterious	None	None	None	None	N
L/D	0.9989	likely_pathogenic	0.9993	pathogenic	-2.75	Highly Destabilizing	0.974	D	0.871	deleterious	None	None	None	None	N
L/E	0.9915	likely_pathogenic	0.994	pathogenic	-2.482	Highly Destabilizing	0.974	D	0.853	deleterious	None	None	None	None	N
L/F	0.448	ambiguous	0.4856	ambiguous	-1.462	Destabilizing	0.934	D	0.697	prob.neutral	D	0.530384598	None	None	N
L/G	0.9858	likely_pathogenic	0.9896	pathogenic	-2.906	Highly Destabilizing	0.974	D	0.837	deleterious	None	None	None	None	N
L/H	0.9882	likely_pathogenic	0.9913	pathogenic	-2.283	Highly Destabilizing	0.997	D	0.864	deleterious	D	0.631471348	None	None	N
L/I	0.1251	likely_benign	0.1276	benign	-0.831	Destabilizing	0.005	N	0.249	neutral	D	0.562001666	None	None	N
L/K	0.9889	likely_pathogenic	0.9917	pathogenic	-1.844	Destabilizing	0.974	D	0.814	deleterious	None	None	None	None	N
L/M	0.1893	likely_benign	0.2015	benign	-0.831	Destabilizing	0.525	D	0.454	neutral	None	None	None	None	N
L/N	0.9956	likely_pathogenic	0.9965	pathogenic	-2.344	Highly Destabilizing	0.991	D	0.877	deleterious	None	None	None	None	N
L/P	0.99	likely_pathogenic	0.9945	pathogenic	-1.334	Destabilizing	0.028	N	0.686	prob.neutral	D	0.631471348	None	None	N
L/Q	0.9778	likely_pathogenic	0.9826	pathogenic	-2.111	Highly Destabilizing	0.974	D	0.859	deleterious	None	None	None	None	N
L/R	0.983	likely_pathogenic	0.9872	pathogenic	-1.792	Destabilizing	0.966	D	0.857	deleterious	D	0.631471348	None	None	N
L/S	0.9912	likely_pathogenic	0.9932	pathogenic	-2.973	Highly Destabilizing	0.974	D	0.81	deleterious	None	None	None	None	N
L/T	0.9493	likely_pathogenic	0.9588	pathogenic	-2.546	Highly Destabilizing	0.842	D	0.728	prob.delet.	None	None	None	None	N
L/V	0.2247	likely_benign	0.2366	benign	-1.334	Destabilizing	0.454	N	0.513	neutral	D	0.532024514	None	None	N
L/W	0.9118	likely_pathogenic	0.936	pathogenic	-1.738	Destabilizing	0.998	D	0.843	deleterious	None	None	None	None	N
L/Y	0.9503	likely_pathogenic	0.9611	pathogenic	-1.465	Destabilizing	0.991	D	0.782	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.