TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4871	14836;14837;14838	chr2:178735835;178735834;178735833	chr2:179600562;179600561;179600560
N2AB	4554	13885;13886;13887	chr2:178735835;178735834;178735833	chr2:179600562;179600561;179600560
N2A	3627	11104;11105;11106	chr2:178735835;178735834;178735833	chr2:179600562;179600561;179600560
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: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-31
• Domain position: 77
• Structural Position: 161
• Q(SASA): 0.1334
• 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
N/K	rs1182104962	None	1.0	D	0.713	0.588	0.27855597813	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.88E-06	0
N/K	rs1182104962	None	1.0	D	0.713	0.588	0.27855597813	gnomAD-3.1.2	6.57E-06	None	None	None	None	I	None	0	0	0	0	0	None	0	0	0	0	4.78469E-04
N/K	rs1182104962	None	1.0	D	0.713	0.588	0.27855597813	gnomAD-4.0.0	6.57229E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	0	4.78469E-04

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
N/A	0.9856	likely_pathogenic	0.9835	pathogenic	-1.137	Destabilizing	1.0	D	0.746	deleterious	None	None	None	None	I
N/C	0.9225	likely_pathogenic	0.9025	pathogenic	-0.353	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	I
N/D	0.9464	likely_pathogenic	0.9401	pathogenic	-1.268	Destabilizing	0.999	D	0.611	neutral	D	0.76427153	None	None	I
N/E	0.9961	likely_pathogenic	0.9952	pathogenic	-1.143	Destabilizing	0.999	D	0.69	prob.neutral	None	None	None	None	I
N/F	0.9988	likely_pathogenic	0.9986	pathogenic	-0.89	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
N/G	0.9492	likely_pathogenic	0.9436	pathogenic	-1.48	Destabilizing	0.999	D	0.557	neutral	None	None	None	None	I
N/H	0.9512	likely_pathogenic	0.942	pathogenic	-1.141	Destabilizing	1.0	D	0.727	prob.delet.	D	0.766670733	None	None	I
N/I	0.9881	likely_pathogenic	0.9871	pathogenic	-0.251	Destabilizing	1.0	D	0.734	prob.delet.	D	0.767405593	None	None	I
N/K	0.9964	likely_pathogenic	0.9955	pathogenic	-0.369	Destabilizing	1.0	D	0.713	prob.delet.	D	0.76576111	None	None	I
N/L	0.9622	likely_pathogenic	0.9579	pathogenic	-0.251	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
N/M	0.9874	likely_pathogenic	0.9862	pathogenic	0.243	Stabilizing	1.0	D	0.74	deleterious	None	None	None	None	I
N/P	0.9936	likely_pathogenic	0.9917	pathogenic	-0.519	Destabilizing	1.0	D	0.73	prob.delet.	None	None	None	None	I
N/Q	0.9944	likely_pathogenic	0.9934	pathogenic	-1.115	Destabilizing	1.0	D	0.733	prob.delet.	None	None	None	None	I
N/R	0.9939	likely_pathogenic	0.9923	pathogenic	-0.34	Destabilizing	1.0	D	0.741	deleterious	None	None	None	None	I
N/S	0.503	ambiguous	0.4894	ambiguous	-1.122	Destabilizing	0.999	D	0.585	neutral	D	0.567967795	None	None	I
N/T	0.884	likely_pathogenic	0.8736	pathogenic	-0.811	Destabilizing	0.999	D	0.681	prob.neutral	D	0.66317436	None	None	I
N/V	0.9779	likely_pathogenic	0.9742	pathogenic	-0.519	Destabilizing	1.0	D	0.737	prob.delet.	None	None	None	None	I
N/W	0.9994	likely_pathogenic	0.9992	pathogenic	-0.628	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	I
N/Y	0.9886	likely_pathogenic	0.9863	pathogenic	-0.394	Destabilizing	1.0	D	0.748	deleterious	D	0.766670733	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.