TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4693	14302;14303;14304	chr2:178739156;178739155;178739154	chr2:179603883;179603882;179603881
N2AB	4376	13351;13352;13353	chr2:178739156;178739155;178739154	chr2:179603883;179603882;179603881
N2A	None	None	chr2:None	chr2:None
N2B	4330	13213;13214;13215	chr2:178739156;178739155;178739154	chr2:179603883;179603882;179603881
Novex-1	4455	13588;13589;13590	chr2:178739156;178739155;178739154	chr2:179603883;179603882;179603881
Novex-2	4522	13789;13790;13791	chr2:178739156;178739155;178739154	chr2:179603883;179603882;179603881
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-29
• Domain position: 88
• Structural Position: 175
• Q(SASA): 0.3512
• 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
T/S	None	None	0.992	D	0.464	0.363	None	gnomAD-4.0.0	7.35882E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	9.4021E-07	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
T/A	0.1248	likely_benign	0.1337	benign	-0.833	Destabilizing	0.992	D	0.485	neutral	D	0.584151158	None	None	N
T/C	0.512	ambiguous	0.5193	ambiguous	-0.602	Destabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	N
T/D	0.4092	ambiguous	0.433	ambiguous	-0.286	Destabilizing	0.996	D	0.686	prob.neutral	None	None	None	None	N
T/E	0.3085	likely_benign	0.3216	benign	-0.275	Destabilizing	0.998	D	0.671	neutral	None	None	None	None	N
T/F	0.2503	likely_benign	0.2527	benign	-0.794	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
T/G	0.3928	ambiguous	0.4336	ambiguous	-1.103	Destabilizing	0.994	D	0.658	neutral	None	None	None	None	N
T/H	0.2254	likely_benign	0.2174	benign	-1.339	Destabilizing	1.0	D	0.796	deleterious	None	None	None	None	N
T/I	0.1874	likely_benign	0.1923	benign	-0.2	Destabilizing	1.0	D	0.789	deleterious	D	0.556181869	None	None	N
T/K	0.2035	likely_benign	0.205	benign	-0.762	Destabilizing	0.998	D	0.675	prob.neutral	None	None	None	None	N
T/L	0.1308	likely_benign	0.1376	benign	-0.2	Destabilizing	0.997	D	0.621	neutral	None	None	None	None	N
T/M	0.1126	likely_benign	0.114	benign	0.033	Stabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
T/N	0.1514	likely_benign	0.1594	benign	-0.709	Destabilizing	0.467	N	0.304	neutral	D	0.586331613	None	None	N
T/P	0.5786	likely_pathogenic	0.6675	pathogenic	-0.379	Destabilizing	1.0	D	0.783	deleterious	D	0.714516039	None	None	N
T/Q	0.2381	likely_benign	0.2357	benign	-0.887	Destabilizing	0.999	D	0.791	deleterious	None	None	None	None	N
T/R	0.153	likely_benign	0.1513	benign	-0.534	Destabilizing	0.998	D	0.791	deleterious	None	None	None	None	N
T/S	0.1403	likely_benign	0.1496	benign	-1.015	Destabilizing	0.992	D	0.464	neutral	D	0.54630057	None	None	N
T/V	0.175	likely_benign	0.181	benign	-0.379	Destabilizing	0.997	D	0.565	neutral	None	None	None	None	N
T/W	0.5739	likely_pathogenic	0.5784	pathogenic	-0.701	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
T/Y	0.2855	likely_benign	0.288	benign	-0.479	Destabilizing	1.0	D	0.812	deleterious	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.