TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15986	48181;48182;48183	chr2:178616933;178616932;178616931	chr2:179481660;179481659;179481658
N2AB	14345	43258;43259;43260	chr2:178616933;178616932;178616931	chr2:179481660;179481659;179481658
N2A	13418	40477;40478;40479	chr2:178616933;178616932;178616931	chr2:179481660;179481659;179481658
N2B	6921	20986;20987;20988	chr2:178616933;178616932;178616931	chr2:179481660;179481659;179481658
Novex-1	7046	21361;21362;21363	chr2:178616933;178616932;178616931	chr2:179481660;179481659;179481658
Novex-2	7113	21562;21563;21564	chr2:178616933;178616932;178616931	chr2:179481660;179481659;179481658
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-109
• Domain position: 19
• Structural Position: 35
• Q(SASA): 0.2616
• 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/G	None	None	0.911	N	0.561	0.168	0.301455362545	gnomAD-4.0.0	1.59334E-06	None	None	None	None	I	None	0	2.28854E-05	None	0	0	None	0	0	0	0	0
S/R	None	None	0.989	N	0.772	0.308	0.320256813643	gnomAD-4.0.0	1.59334E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.43324E-05	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	0.0821	likely_benign	0.0869	benign	-0.537	Destabilizing	0.49	N	0.414	neutral	None	None	None	None	I
S/C	0.0532	likely_benign	0.0605	benign	-0.381	Destabilizing	0.989	D	0.755	deleterious	N	0.510168819	None	None	I
S/D	0.9378	likely_pathogenic	0.9528	pathogenic	0.102	Stabilizing	0.971	D	0.606	neutral	None	None	None	None	I
S/E	0.9003	likely_pathogenic	0.9254	pathogenic	0.065	Stabilizing	0.971	D	0.61	neutral	None	None	None	None	I
S/F	0.2312	likely_benign	0.29	benign	-0.899	Destabilizing	0.842	D	0.762	deleterious	None	None	None	None	I
S/G	0.2667	likely_benign	0.2898	benign	-0.74	Destabilizing	0.911	D	0.561	neutral	N	0.510168819	None	None	I
S/H	0.6987	likely_pathogenic	0.7357	pathogenic	-1.283	Destabilizing	0.991	D	0.75	deleterious	None	None	None	None	I
S/I	0.0761	likely_benign	0.1198	benign	-0.118	Destabilizing	0.002	N	0.417	neutral	N	0.368822375	None	None	I
S/K	0.9654	likely_pathogenic	0.9762	pathogenic	-0.558	Destabilizing	0.915	D	0.609	neutral	None	None	None	None	I
S/L	0.1129	likely_benign	0.155	benign	-0.118	Destabilizing	0.325	N	0.497	neutral	None	None	None	None	I
S/M	0.1419	likely_benign	0.1784	benign	0.101	Stabilizing	0.949	D	0.774	deleterious	None	None	None	None	I
S/N	0.5531	ambiguous	0.5849	pathogenic	-0.428	Destabilizing	0.961	D	0.614	neutral	N	0.505160246	None	None	I
S/P	0.8826	likely_pathogenic	0.9282	pathogenic	-0.224	Destabilizing	0.991	D	0.777	deleterious	None	None	None	None	I
S/Q	0.8487	likely_pathogenic	0.8661	pathogenic	-0.59	Destabilizing	0.991	D	0.686	prob.neutral	None	None	None	None	I
S/R	0.9379	likely_pathogenic	0.9558	pathogenic	-0.465	Destabilizing	0.989	D	0.772	deleterious	N	0.510168819	None	None	I
S/T	0.1131	likely_benign	0.1183	benign	-0.474	Destabilizing	0.625	D	0.565	neutral	N	0.501485134	None	None	I
S/V	0.0868	likely_benign	0.1139	benign	-0.224	Destabilizing	0.325	N	0.497	neutral	None	None	None	None	I
S/W	0.5897	likely_pathogenic	0.6538	pathogenic	-0.889	Destabilizing	0.998	D	0.787	deleterious	None	None	None	None	I
S/Y	0.2724	likely_benign	0.3251	benign	-0.608	Destabilizing	0.991	D	0.783	deleterious	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.