TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	981	3166;3167;3168	chr2:178782965;178782964;178782963	chr2:179647692;179647691;179647690
N2AB	981	3166;3167;3168	chr2:178782965;178782964;178782963	chr2:179647692;179647691;179647690
N2A	981	3166;3167;3168	chr2:178782965;178782964;178782963	chr2:179647692;179647691;179647690
N2B	935	3028;3029;3030	chr2:178782965;178782964;178782963	chr2:179647692;179647691;179647690
Novex-1	935	3028;3029;3030	chr2:178782965;178782964;178782963	chr2:179647692;179647691;179647690
Novex-2	935	3028;3029;3030	chr2:178782965;178782964;178782963	chr2:179647692;179647691;179647690
Novex-3	981	3166;3167;3168	chr2:178782965;178782964;178782963	chr2:179647692;179647691;179647690

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAC
• RefSeq wild type template codon: ATG
• Domain: Ig-3
• Domain position: 39
• Structural Position: 55
• Q(SASA): 0.7247
• Predicted PPI site: N

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
Y/C	rs1312572604	0.219	1.0	N	0.663	0.583	0.696195976467	gnomAD-2.1.1	3.99E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	4.62E-05	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
Y/A	0.9207	likely_pathogenic	0.9257	pathogenic	-0.557	Destabilizing	1.0	D	0.589	neutral	None	None	None	None	N
Y/C	0.6933	likely_pathogenic	0.7178	pathogenic	0.125	Stabilizing	1.0	D	0.663	neutral	N	0.493779559	None	None	N
Y/D	0.8276	likely_pathogenic	0.8473	pathogenic	0.727	Stabilizing	1.0	D	0.689	prob.neutral	N	0.39562811	None	None	N
Y/E	0.956	likely_pathogenic	0.9609	pathogenic	0.712	Stabilizing	1.0	D	0.667	neutral	None	None	None	None	N
Y/F	0.2588	likely_benign	0.2451	benign	-0.227	Destabilizing	0.999	D	0.57	neutral	N	0.459565853	None	None	N
Y/G	0.8935	likely_pathogenic	0.907	pathogenic	-0.74	Destabilizing	1.0	D	0.687	prob.neutral	None	None	None	None	N
Y/H	0.7677	likely_pathogenic	0.7763	pathogenic	0.265	Stabilizing	1.0	D	0.643	neutral	N	0.436124171	None	None	N
Y/I	0.8834	likely_pathogenic	0.8839	pathogenic	-0.097	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	N
Y/K	0.9627	likely_pathogenic	0.9653	pathogenic	0.163	Stabilizing	1.0	D	0.664	neutral	None	None	None	None	N
Y/L	0.8254	likely_pathogenic	0.834	pathogenic	-0.097	Destabilizing	0.999	D	0.645	neutral	None	None	None	None	N
Y/M	0.9115	likely_pathogenic	0.9147	pathogenic	-0.096	Destabilizing	1.0	D	0.651	neutral	None	None	None	None	N
Y/N	0.6896	likely_pathogenic	0.7049	pathogenic	-0.085	Destabilizing	1.0	D	0.67	neutral	N	0.424363004	None	None	N
Y/P	0.9957	likely_pathogenic	0.9961	pathogenic	-0.232	Destabilizing	1.0	D	0.684	prob.neutral	None	None	None	None	N
Y/Q	0.9466	likely_pathogenic	0.9519	pathogenic	-0.008	Destabilizing	1.0	D	0.667	neutral	None	None	None	None	N
Y/R	0.9048	likely_pathogenic	0.9122	pathogenic	0.348	Stabilizing	1.0	D	0.675	neutral	None	None	None	None	N
Y/S	0.6934	likely_pathogenic	0.7176	pathogenic	-0.431	Destabilizing	1.0	D	0.671	neutral	N	0.363944507	None	None	N
Y/T	0.8717	likely_pathogenic	0.8775	pathogenic	-0.356	Destabilizing	1.0	D	0.665	neutral	None	None	None	None	N
Y/V	0.8085	likely_pathogenic	0.812	pathogenic	-0.232	Destabilizing	1.0	D	0.617	neutral	None	None	None	None	N
Y/W	0.8067	likely_pathogenic	0.8072	pathogenic	-0.379	Destabilizing	1.0	D	0.643	neutral	None	None	None	None	N

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.