TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21591	64996;64997;64998	chr2:178584870;178584869;178584868	chr2:179449597;179449596;179449595
N2AB	19950	60073;60074;60075	chr2:178584870;178584869;178584868	chr2:179449597;179449596;179449595
N2A	19023	57292;57293;57294	chr2:178584870;178584869;178584868	chr2:179449597;179449596;179449595
N2B	12526	37801;37802;37803	chr2:178584870;178584869;178584868	chr2:179449597;179449596;179449595
Novex-1	12651	38176;38177;38178	chr2:178584870;178584869;178584868	chr2:179449597;179449596;179449595
Novex-2	12718	38377;38378;38379	chr2:178584870;178584869;178584868	chr2:179449597;179449596;179449595
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: Fn3-44
• Domain position: 33
• Structural Position: 34
• Q(SASA): 0.7543
• 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/Y	None	None	0.983	N	0.717	0.303	0.422160833541	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-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
N/A	0.1933	likely_benign	0.1672	benign	-0.187	Destabilizing	0.633	D	0.609	neutral	None	None	None	None	I
N/C	0.2533	likely_benign	0.2178	benign	0.362	Stabilizing	0.989	D	0.736	prob.delet.	None	None	None	None	I
N/D	0.2602	likely_benign	0.2294	benign	0.138	Stabilizing	0.722	D	0.611	neutral	N	0.451773807	None	None	I
N/E	0.5674	likely_pathogenic	0.4882	ambiguous	0.076	Stabilizing	0.633	D	0.624	neutral	None	None	None	None	I
N/F	0.6173	likely_pathogenic	0.5371	ambiguous	-0.739	Destabilizing	0.961	D	0.725	prob.delet.	None	None	None	None	I
N/G	0.2905	likely_benign	0.2595	benign	-0.299	Destabilizing	0.011	N	0.173	neutral	None	None	None	None	I
N/H	0.1491	likely_benign	0.1274	benign	-0.38	Destabilizing	0.949	D	0.615	neutral	N	0.482790147	None	None	I
N/I	0.2594	likely_benign	0.2129	benign	0.008	Stabilizing	0.901	D	0.745	deleterious	N	0.489697477	None	None	I
N/K	0.5656	likely_pathogenic	0.4748	ambiguous	0.217	Stabilizing	0.565	D	0.613	neutral	N	0.44638663	None	None	I
N/L	0.2792	likely_benign	0.2317	benign	0.008	Stabilizing	0.923	D	0.664	neutral	None	None	None	None	I
N/M	0.3729	ambiguous	0.3162	benign	0.299	Stabilizing	0.996	D	0.701	prob.neutral	None	None	None	None	I
N/P	0.3821	ambiguous	0.3178	benign	-0.033	Destabilizing	0.961	D	0.726	prob.delet.	None	None	None	None	I
N/Q	0.4388	ambiguous	0.364	ambiguous	-0.173	Destabilizing	0.923	D	0.627	neutral	None	None	None	None	I
N/R	0.5741	likely_pathogenic	0.504	ambiguous	0.275	Stabilizing	0.923	D	0.615	neutral	None	None	None	None	I
N/S	0.081	likely_benign	0.0779	benign	0.071	Stabilizing	0.008	N	0.3	neutral	N	0.427339509	None	None	I
N/T	0.144	likely_benign	0.1267	benign	0.131	Stabilizing	0.565	D	0.613	neutral	N	0.460374648	None	None	I
N/V	0.2139	likely_benign	0.1867	benign	-0.033	Destabilizing	0.923	D	0.724	prob.delet.	None	None	None	None	I
N/W	0.8416	likely_pathogenic	0.8045	pathogenic	-0.813	Destabilizing	0.996	D	0.753	deleterious	None	None	None	None	I
N/Y	0.2615	likely_benign	0.2199	benign	-0.505	Destabilizing	0.983	D	0.717	prob.delet.	N	0.493911218	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.