TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7165	21718;21719;21720	chr2:178723607;178723606;178723605	chr2:179588334;179588333;179588332
N2AB	6848	20767;20768;20769	chr2:178723607;178723606;178723605	chr2:179588334;179588333;179588332
N2A	5921	17986;17987;17988	chr2:178723607;178723606;178723605	chr2:179588334;179588333;179588332
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-56
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.7422
• 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
P/L	rs1370391729	0.107	1.0	N	0.69	0.436	0.811862050649	gnomAD-2.1.1	4.04E-06	None	None	None	None	I	None	0	2.91E-05	None	0	0	None	0	None	0	0	0
P/L	rs1370391729	0.107	1.0	N	0.69	0.436	0.811862050649	gnomAD-4.0.0	1.59299E-06	None	None	None	None	I	None	0	2.29022E-05	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
P/A	0.1983	likely_benign	0.223	benign	-0.51	Destabilizing	1.0	D	0.665	neutral	N	0.488642071	None	None	I
P/C	0.7705	likely_pathogenic	0.8172	pathogenic	-0.553	Destabilizing	1.0	D	0.671	neutral	None	None	None	None	I
P/D	0.6053	likely_pathogenic	0.6294	pathogenic	-0.415	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
P/E	0.4749	ambiguous	0.5141	ambiguous	-0.51	Destabilizing	1.0	D	0.669	neutral	None	None	None	None	I
P/F	0.7409	likely_pathogenic	0.7795	pathogenic	-0.698	Destabilizing	1.0	D	0.631	neutral	None	None	None	None	I
P/G	0.5603	ambiguous	0.5819	pathogenic	-0.655	Destabilizing	1.0	D	0.723	prob.delet.	None	None	None	None	I
P/H	0.4285	ambiguous	0.4728	ambiguous	-0.215	Destabilizing	1.0	D	0.64	neutral	None	None	None	None	I
P/I	0.5561	ambiguous	0.612	pathogenic	-0.264	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	I
P/K	0.5975	likely_pathogenic	0.6301	pathogenic	-0.471	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	I
P/L	0.2793	likely_benign	0.3252	benign	-0.264	Destabilizing	1.0	D	0.69	prob.neutral	N	0.500683166	None	None	I
P/M	0.5845	likely_pathogenic	0.6406	pathogenic	-0.422	Destabilizing	1.0	D	0.644	neutral	None	None	None	None	I
P/N	0.543	ambiguous	0.5779	pathogenic	-0.17	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
P/Q	0.3691	ambiguous	0.4184	ambiguous	-0.392	Destabilizing	1.0	D	0.644	neutral	N	0.488931559	None	None	I
P/R	0.3877	ambiguous	0.421	ambiguous	0.02	Stabilizing	1.0	D	0.673	neutral	N	0.495745642	None	None	I
P/S	0.2727	likely_benign	0.3079	benign	-0.507	Destabilizing	1.0	D	0.681	prob.neutral	N	0.501568539	None	None	I
P/T	0.2372	likely_benign	0.2708	benign	-0.501	Destabilizing	1.0	D	0.675	neutral	D	0.533864834	None	None	I
P/V	0.4045	ambiguous	0.4509	ambiguous	-0.312	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
P/W	0.8667	likely_pathogenic	0.8881	pathogenic	-0.792	Destabilizing	1.0	D	0.681	prob.neutral	None	None	None	None	I
P/Y	0.6999	likely_pathogenic	0.7326	pathogenic	-0.493	Destabilizing	1.0	D	0.642	neutral	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.