TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29582	88969;88970;88971	chr2:178554603;178554602;178554601	chr2:179419330;179419329;179419328
N2AB	27941	84046;84047;84048	chr2:178554603;178554602;178554601	chr2:179419330;179419329;179419328
N2A	27014	81265;81266;81267	chr2:178554603;178554602;178554601	chr2:179419330;179419329;179419328
N2B	20517	61774;61775;61776	chr2:178554603;178554602;178554601	chr2:179419330;179419329;179419328
Novex-1	20642	62149;62150;62151	chr2:178554603;178554602;178554601	chr2:179419330;179419329;179419328
Novex-2	20709	62350;62351;62352	chr2:178554603;178554602;178554601	chr2:179419330;179419329;179419328
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: Fn3-103
• Domain position: 50
• Structural Position: 66
• Q(SASA): 0.439
• 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/C	None	None	1.0	N	0.679	0.383	0.583395719892	gnomAD-4.0.0	1.59102E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85776E-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	0.1569	likely_benign	0.1619	benign	-0.524	Destabilizing	0.973	D	0.395	neutral	N	0.448792217	None	None	I
S/C	0.2549	likely_benign	0.2699	benign	-0.393	Destabilizing	1.0	D	0.679	prob.neutral	N	0.469420228	None	None	I
S/D	0.8953	likely_pathogenic	0.9148	pathogenic	0.183	Stabilizing	1.0	D	0.569	neutral	None	None	None	None	I
S/E	0.914	likely_pathogenic	0.9265	pathogenic	0.161	Stabilizing	0.999	D	0.543	neutral	None	None	None	None	I
S/F	0.6792	likely_pathogenic	0.7235	pathogenic	-0.749	Destabilizing	0.998	D	0.713	prob.delet.	N	0.45135252	None	None	I
S/G	0.2105	likely_benign	0.2159	benign	-0.744	Destabilizing	0.999	D	0.481	neutral	None	None	None	None	I
S/H	0.778	likely_pathogenic	0.7998	pathogenic	-1.084	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
S/I	0.5283	ambiguous	0.5596	ambiguous	-0.056	Destabilizing	0.983	D	0.575	neutral	None	None	None	None	I
S/K	0.9751	likely_pathogenic	0.9792	pathogenic	-0.583	Destabilizing	0.999	D	0.544	neutral	None	None	None	None	I
S/L	0.304	likely_benign	0.3254	benign	-0.056	Destabilizing	0.983	D	0.517	neutral	None	None	None	None	I
S/M	0.3856	ambiguous	0.3975	ambiguous	-0.002	Destabilizing	1.0	D	0.678	prob.neutral	None	None	None	None	I
S/N	0.3898	ambiguous	0.4024	ambiguous	-0.47	Destabilizing	1.0	D	0.587	neutral	None	None	None	None	I
S/P	0.9581	likely_pathogenic	0.9621	pathogenic	-0.178	Destabilizing	0.999	D	0.691	prob.neutral	N	0.46840627	None	None	I
S/Q	0.8482	likely_pathogenic	0.8554	pathogenic	-0.586	Destabilizing	1.0	D	0.629	neutral	None	None	None	None	I
S/R	0.9641	likely_pathogenic	0.9703	pathogenic	-0.425	Destabilizing	1.0	D	0.693	prob.neutral	None	None	None	None	I
S/T	0.1497	likely_benign	0.1447	benign	-0.526	Destabilizing	0.989	D	0.483	neutral	N	0.389706628	None	None	I
S/V	0.4533	ambiguous	0.4725	ambiguous	-0.178	Destabilizing	0.611	D	0.356	neutral	None	None	None	None	I
S/W	0.7534	likely_pathogenic	0.8005	pathogenic	-0.762	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
S/Y	0.5835	likely_pathogenic	0.6271	pathogenic	-0.487	Destabilizing	0.999	D	0.718	prob.delet.	N	0.475402815	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.