TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24474	73645;73646;73647	chr2:178572712;178572711;178572710	chr2:179437439;179437438;179437437
N2AB	22833	68722;68723;68724	chr2:178572712;178572711;178572710	chr2:179437439;179437438;179437437
N2A	21906	65941;65942;65943	chr2:178572712;178572711;178572710	chr2:179437439;179437438;179437437
N2B	15409	46450;46451;46452	chr2:178572712;178572711;178572710	chr2:179437439;179437438;179437437
Novex-1	15534	46825;46826;46827	chr2:178572712;178572711;178572710	chr2:179437439;179437438;179437437
Novex-2	15601	47026;47027;47028	chr2:178572712;178572711;178572710	chr2:179437439;179437438;179437437
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-132
• Domain position: 44
• Structural Position: 122
• Q(SASA): 0.3093
• 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/N	None	None	0.012	N	0.12	0.104	0.192905019026	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	0.0723	likely_benign	0.0763	benign	-0.35	Destabilizing	0.373	N	0.335	neutral	None	None	None	None	N
S/C	0.0996	likely_benign	0.1033	benign	-0.367	Destabilizing	0.994	D	0.399	neutral	N	0.519476958	None	None	N
S/D	0.2477	likely_benign	0.2596	benign	0.479	Stabilizing	0.59	D	0.269	neutral	None	None	None	None	N
S/E	0.3415	ambiguous	0.353	ambiguous	0.43	Stabilizing	0.742	D	0.284	neutral	None	None	None	None	N
S/F	0.1606	likely_benign	0.1755	benign	-0.766	Destabilizing	0.953	D	0.473	neutral	None	None	None	None	N
S/G	0.094	likely_benign	0.0951	benign	-0.522	Destabilizing	0.472	N	0.291	neutral	N	0.48932741	None	None	N
S/H	0.2169	likely_benign	0.2313	benign	-0.949	Destabilizing	0.953	D	0.401	neutral	None	None	None	None	N
S/I	0.1006	likely_benign	0.1044	benign	-0.022	Destabilizing	0.884	D	0.435	neutral	N	0.447846147	None	None	N
S/K	0.4657	ambiguous	0.4811	ambiguous	-0.38	Destabilizing	0.373	N	0.292	neutral	None	None	None	None	N
S/L	0.0913	likely_benign	0.0975	benign	-0.022	Destabilizing	0.59	D	0.429	neutral	None	None	None	None	N
S/M	0.1326	likely_benign	0.1503	benign	-0.022	Destabilizing	0.984	D	0.403	neutral	None	None	None	None	N
S/N	0.0762	likely_benign	0.0809	benign	-0.248	Destabilizing	0.012	N	0.12	neutral	N	0.442610898	None	None	N
S/P	0.66	likely_pathogenic	0.6525	pathogenic	-0.099	Destabilizing	0.953	D	0.373	neutral	None	None	None	None	N
S/Q	0.3078	likely_benign	0.3274	benign	-0.379	Destabilizing	0.91	D	0.346	neutral	None	None	None	None	N
S/R	0.4164	ambiguous	0.423	ambiguous	-0.28	Destabilizing	0.007	N	0.255	neutral	N	0.445939205	None	None	N
S/T	0.0599	likely_benign	0.0645	benign	-0.328	Destabilizing	0.012	N	0.115	neutral	N	0.438802589	None	None	N
S/V	0.1066	likely_benign	0.1138	benign	-0.099	Destabilizing	0.59	D	0.403	neutral	None	None	None	None	N
S/W	0.3387	likely_benign	0.3428	ambiguous	-0.788	Destabilizing	0.996	D	0.561	neutral	None	None	None	None	N
S/Y	0.153	likely_benign	0.1666	benign	-0.484	Destabilizing	0.984	D	0.471	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.