TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	29894	89905;89906;89907	chr2:178553220;178553219;178553218	chr2:179417947;179417946;179417945
N2AB	28253	84982;84983;84984	chr2:178553220;178553219;178553218	chr2:179417947;179417946;179417945
N2A	27326	82201;82202;82203	chr2:178553220;178553219;178553218	chr2:179417947;179417946;179417945
N2B	20829	62710;62711;62712	chr2:178553220;178553219;178553218	chr2:179417947;179417946;179417945
Novex-1	20954	63085;63086;63087	chr2:178553220;178553219;178553218	chr2:179417947;179417946;179417945
Novex-2	21021	63286;63287;63288	chr2:178553220;178553219;178553218	chr2:179417947;179417946;179417945
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCC
• RefSeq wild type template codon: AGG
• Domain: Ig-147
• Domain position: 53
• Structural Position: 135
• Q(SASA): 0.1538
• 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
S/A	None	None	0.333	N	0.26	0.116	0.258283824007	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	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
S/A	0.1123	likely_benign	0.0926	benign	-0.882	Destabilizing	0.333	N	0.26	neutral	N	0.490538131	None	None	N
S/C	0.112	likely_benign	0.0974	benign	-0.637	Destabilizing	1.0	D	0.691	prob.neutral	N	0.487987415	None	None	N
S/D	0.768	likely_pathogenic	0.6835	pathogenic	-0.351	Destabilizing	0.999	D	0.605	neutral	None	None	None	None	N
S/E	0.7364	likely_pathogenic	0.6815	pathogenic	-0.314	Destabilizing	0.996	D	0.567	neutral	None	None	None	None	N
S/F	0.2261	likely_benign	0.1728	benign	-1.061	Destabilizing	0.999	D	0.733	prob.delet.	N	0.454214758	None	None	N
S/G	0.1704	likely_benign	0.1365	benign	-1.148	Destabilizing	0.98	D	0.5	neutral	None	None	None	None	N
S/H	0.3637	ambiguous	0.3315	benign	-1.624	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
S/I	0.3114	likely_benign	0.2418	benign	-0.267	Destabilizing	0.999	D	0.715	prob.delet.	None	None	None	None	N
S/K	0.7916	likely_pathogenic	0.7436	pathogenic	-0.531	Destabilizing	0.996	D	0.565	neutral	None	None	None	None	N
S/L	0.1581	likely_benign	0.1272	benign	-0.267	Destabilizing	0.992	D	0.622	neutral	None	None	None	None	N
S/M	0.2589	likely_benign	0.2204	benign	-0.07	Destabilizing	1.0	D	0.691	prob.neutral	None	None	None	None	N
S/N	0.3122	likely_benign	0.2579	benign	-0.629	Destabilizing	1.0	D	0.598	neutral	None	None	None	None	N
S/P	0.9753	likely_pathogenic	0.9555	pathogenic	-0.439	Destabilizing	0.998	D	0.72	prob.delet.	N	0.492506866	None	None	N
S/Q	0.5569	ambiguous	0.533	ambiguous	-0.735	Destabilizing	1.0	D	0.655	neutral	None	None	None	None	N
S/R	0.6772	likely_pathogenic	0.6214	pathogenic	-0.554	Destabilizing	0.999	D	0.727	prob.delet.	None	None	None	None	N
S/T	0.1176	likely_benign	0.1002	benign	-0.624	Destabilizing	0.989	D	0.501	neutral	N	0.474491243	None	None	N
S/V	0.2734	likely_benign	0.2169	benign	-0.439	Destabilizing	0.992	D	0.64	neutral	None	None	None	None	N
S/W	0.4059	ambiguous	0.3574	ambiguous	-1.039	Destabilizing	1.0	D	0.697	prob.neutral	None	None	None	None	N
S/Y	0.163	likely_benign	0.1323	benign	-0.74	Destabilizing	0.999	D	0.727	prob.delet.	N	0.44713407	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.