TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24097	72514;72515;72516	chr2:178573843;178573842;178573841	chr2:179438570;179438569;179438568
N2AB	22456	67591;67592;67593	chr2:178573843;178573842;178573841	chr2:179438570;179438569;179438568
N2A	21529	64810;64811;64812	chr2:178573843;178573842;178573841	chr2:179438570;179438569;179438568
N2B	15032	45319;45320;45321	chr2:178573843;178573842;178573841	chr2:179438570;179438569;179438568
Novex-1	15157	45694;45695;45696	chr2:178573843;178573842;178573841	chr2:179438570;179438569;179438568
Novex-2	15224	45895;45896;45897	chr2:178573843;178573842;178573841	chr2:179438570;179438569;179438568
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-131
• Domain position: 69
• Structural Position: 151
• Q(SASA): 0.3188
• 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	0.117	N	0.532	0.287	0.251639045875	gnomAD-4.0.0	2.05543E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.73732E-04	9.00575E-07	0	1.65898E-05

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	0.1206	likely_benign	0.1298	benign	-0.826	Destabilizing	0.016	N	0.317	neutral	None	None	None	None	N
S/C	0.1405	likely_benign	0.1642	benign	-0.617	Destabilizing	0.915	D	0.523	neutral	D	0.531744024	None	None	N
S/D	0.7477	likely_pathogenic	0.8265	pathogenic	-0.224	Destabilizing	0.149	N	0.517	neutral	None	None	None	None	N
S/E	0.8042	likely_pathogenic	0.8472	pathogenic	-0.223	Destabilizing	0.262	N	0.489	neutral	None	None	None	None	N
S/F	0.717	likely_pathogenic	0.7652	pathogenic	-1.066	Destabilizing	0.791	D	0.56	neutral	None	None	None	None	N
S/G	0.0489	likely_benign	0.0601	benign	-1.065	Destabilizing	None	N	0.142	neutral	N	0.496928173	None	None	N
S/H	0.6566	likely_pathogenic	0.703	pathogenic	-1.51	Destabilizing	0.791	D	0.545	neutral	None	None	None	None	N
S/I	0.5548	ambiguous	0.6426	pathogenic	-0.293	Destabilizing	0.484	N	0.575	neutral	N	0.517411977	None	None	N
S/K	0.841	likely_pathogenic	0.8835	pathogenic	-0.643	Destabilizing	0.149	N	0.489	neutral	None	None	None	None	N
S/L	0.3552	ambiguous	0.406	ambiguous	-0.293	Destabilizing	0.149	N	0.559	neutral	None	None	None	None	N
S/M	0.4311	ambiguous	0.4877	ambiguous	0.005	Stabilizing	0.935	D	0.536	neutral	None	None	None	None	N
S/N	0.3509	ambiguous	0.4045	ambiguous	-0.654	Destabilizing	0.117	N	0.532	neutral	N	0.500762526	None	None	N
S/P	0.948	likely_pathogenic	0.9512	pathogenic	-0.438	Destabilizing	0.555	D	0.561	neutral	None	None	None	None	N
S/Q	0.7048	likely_pathogenic	0.7516	pathogenic	-0.82	Destabilizing	0.555	D	0.545	neutral	None	None	None	None	N
S/R	0.7288	likely_pathogenic	0.7991	pathogenic	-0.538	Destabilizing	0.484	N	0.562	neutral	N	0.497470843	None	None	N
S/T	0.1039	likely_benign	0.1263	benign	-0.701	Destabilizing	0.117	N	0.527	neutral	N	0.51687937	None	None	N
S/V	0.5256	ambiguous	0.6227	pathogenic	-0.438	Destabilizing	0.262	N	0.548	neutral	None	None	None	None	N
S/W	0.7759	likely_pathogenic	0.8202	pathogenic	-1.007	Destabilizing	0.935	D	0.573	neutral	None	None	None	None	N
S/Y	0.6002	likely_pathogenic	0.6574	pathogenic	-0.74	Destabilizing	0.791	D	0.567	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.