TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27351	82276;82277;82278	chr2:178564081;178564080;178564079	chr2:179428808;179428807;179428806
N2AB	25710	77353;77354;77355	chr2:178564081;178564080;178564079	chr2:179428808;179428807;179428806
N2A	24783	74572;74573;74574	chr2:178564081;178564080;178564079	chr2:179428808;179428807;179428806
N2B	18286	55081;55082;55083	chr2:178564081;178564080;178564079	chr2:179428808;179428807;179428806
Novex-1	18411	55456;55457;55458	chr2:178564081;178564080;178564079	chr2:179428808;179428807;179428806
Novex-2	18478	55657;55658;55659	chr2:178564081;178564080;178564079	chr2:179428808;179428807;179428806
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-140
• Domain position: 74
• Structural Position: 158
• Q(SASA): 0.1761
• Predicted PPI site: I

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/H	None	None	1.0	D	0.841	0.596	0.882090980265	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	6.07533E-05	0
L/V	rs1398866994	-1.626	0.996	N	0.637	0.298	0.596316647014	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	6.46E-05	0	None	0	0	None	0	None	0	0	0
L/V	rs1398866994	-1.626	0.996	N	0.637	0.298	0.596316647014	gnomAD-4.0.0	1.59123E-06	None	None	None	None	I	None	5.65547E-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	0.6258	likely_pathogenic	0.6349	pathogenic	-2.455	Highly Destabilizing	0.813	D	0.447	neutral	None	None	None	None	I
L/C	0.741	likely_pathogenic	0.7538	pathogenic	-1.96	Destabilizing	1.0	D	0.809	deleterious	None	None	None	None	I
L/D	0.9982	likely_pathogenic	0.9985	pathogenic	-2.281	Highly Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
L/E	0.9903	likely_pathogenic	0.9918	pathogenic	-2.143	Highly Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	I
L/F	0.7274	likely_pathogenic	0.7728	pathogenic	-1.582	Destabilizing	1.0	D	0.838	deleterious	N	0.515673549	None	None	I
L/G	0.9514	likely_pathogenic	0.9587	pathogenic	-2.933	Highly Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	I
L/H	0.9846	likely_pathogenic	0.9866	pathogenic	-2.2	Highly Destabilizing	1.0	D	0.841	deleterious	D	0.527536834	None	None	I
L/I	0.1461	likely_benign	0.1624	benign	-1.123	Destabilizing	0.998	D	0.601	neutral	N	0.481209332	None	None	I
L/K	0.9915	likely_pathogenic	0.9926	pathogenic	-1.862	Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	I
L/M	0.2636	likely_benign	0.2766	benign	-1.098	Destabilizing	1.0	D	0.795	deleterious	None	None	None	None	I
L/N	0.9872	likely_pathogenic	0.9884	pathogenic	-1.961	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	I
L/P	0.9952	likely_pathogenic	0.9965	pathogenic	-1.542	Destabilizing	0.999	D	0.848	deleterious	D	0.527283344	None	None	I
L/Q	0.9636	likely_pathogenic	0.9677	pathogenic	-1.973	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	I
L/R	0.978	likely_pathogenic	0.9813	pathogenic	-1.4	Destabilizing	0.999	D	0.845	deleterious	D	0.527283344	None	None	I
L/S	0.9395	likely_pathogenic	0.9486	pathogenic	-2.718	Highly Destabilizing	0.998	D	0.803	deleterious	None	None	None	None	I
L/T	0.8127	likely_pathogenic	0.8305	pathogenic	-2.439	Highly Destabilizing	0.999	D	0.787	deleterious	None	None	None	None	I
L/V	0.1278	likely_benign	0.1326	benign	-1.542	Destabilizing	0.996	D	0.637	neutral	N	0.458804141	None	None	I
L/W	0.9747	likely_pathogenic	0.9819	pathogenic	-1.795	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	I
L/Y	0.9614	likely_pathogenic	0.9687	pathogenic	-1.556	Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	I

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.