TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	7825	23698;23699;23700	chr2:178720169;178720168;178720167	chr2:179584896;179584895;179584894
N2AB	7508	22747;22748;22749	chr2:178720169;178720168;178720167	chr2:179584896;179584895;179584894
N2A	6581	19966;19967;19968	chr2:178720169;178720168;178720167	chr2:179584896;179584895;179584894
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: S
• RefSeq wild type transcript codon: TCT
• RefSeq wild type template codon: AGA
• Domain: Ig-63
• Domain position: 31
• Structural Position: 45
• Q(SASA): 0.4344
• 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
S/Y	None	None	0.986	D	0.773	0.58	0.822358949125	gnomAD-4.0.0	1.59147E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85868E-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
S/A	0.1148	likely_benign	0.1057	benign	-0.443	Destabilizing	None	N	0.239	neutral	N	0.493761087	None	None	I
S/C	0.3506	ambiguous	0.3	benign	-0.341	Destabilizing	0.959	D	0.674	neutral	D	0.526566237	None	None	I
S/D	0.6677	likely_pathogenic	0.5929	pathogenic	0.184	Stabilizing	0.538	D	0.505	neutral	None	None	None	None	I
S/E	0.7243	likely_pathogenic	0.6466	pathogenic	0.233	Stabilizing	0.62	D	0.503	neutral	None	None	None	None	I
S/F	0.3606	ambiguous	0.244	benign	-0.691	Destabilizing	0.959	D	0.775	deleterious	N	0.519564797	None	None	I
S/G	0.2231	likely_benign	0.204	benign	-0.709	Destabilizing	0.52	D	0.511	neutral	None	None	None	None	I
S/H	0.5745	likely_pathogenic	0.4862	ambiguous	-1.052	Destabilizing	0.997	D	0.674	neutral	None	None	None	None	I
S/I	0.4126	ambiguous	0.3293	benign	0.163	Stabilizing	0.939	D	0.741	deleterious	None	None	None	None	I
S/K	0.8955	likely_pathogenic	0.8502	pathogenic	-0.223	Destabilizing	0.813	D	0.507	neutral	None	None	None	None	I
S/L	0.1894	likely_benign	0.156	benign	0.163	Stabilizing	0.686	D	0.641	neutral	None	None	None	None	I
S/M	0.3358	likely_benign	0.2695	benign	0.024	Stabilizing	0.992	D	0.685	prob.neutral	None	None	None	None	I
S/N	0.3159	likely_benign	0.2713	benign	-0.41	Destabilizing	0.12	N	0.515	neutral	None	None	None	None	I
S/P	0.9296	likely_pathogenic	0.8969	pathogenic	-0.004	Destabilizing	0.862	D	0.683	prob.neutral	D	0.526059258	None	None	I
S/Q	0.7082	likely_pathogenic	0.6484	pathogenic	-0.362	Destabilizing	0.969	D	0.576	neutral	None	None	None	None	I
S/R	0.8359	likely_pathogenic	0.7874	pathogenic	-0.285	Destabilizing	0.939	D	0.699	prob.neutral	None	None	None	None	I
S/T	0.0959	likely_benign	0.0855	benign	-0.354	Destabilizing	None	N	0.206	neutral	N	0.47335788	None	None	I
S/V	0.353	ambiguous	0.2808	benign	-0.004	Destabilizing	0.449	N	0.666	neutral	None	None	None	None	I
S/W	0.6206	likely_pathogenic	0.4993	ambiguous	-0.802	Destabilizing	0.997	D	0.773	deleterious	None	None	None	None	I
S/Y	0.344	ambiguous	0.2422	benign	-0.422	Destabilizing	0.986	D	0.773	deleterious	D	0.526059258	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.