TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35679	107260;107261;107262	chr2:178528716;178528715;178528714	chr2:179393443;179393442;179393441
N2AB	34038	102337;102338;102339	chr2:178528716;178528715;178528714	chr2:179393443;179393442;179393441
N2A	33111	99556;99557;99558	chr2:178528716;178528715;178528714	chr2:179393443;179393442;179393441
N2B	26614	80065;80066;80067	chr2:178528716;178528715;178528714	chr2:179393443;179393442;179393441
Novex-1	26739	80440;80441;80442	chr2:178528716;178528715;178528714	chr2:179393443;179393442;179393441
Novex-2	26806	80641;80642;80643	chr2:178528716;178528715;178528714	chr2:179393443;179393442;179393441
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-167
• Domain position: 73
• Structural Position: 158
• Q(SASA): 0.094
• 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/G	rs2154131258	None	None	N	0.337	0.139	0.0884992946249	gnomAD-4.0.0	1.59189E-06	None	None	None	None	N	None	0	0	None	0	2.77331E-05	None	0	0	0	0	0
S/N	None	None	0.001	N	0.414	0.128	0.198526703765	gnomAD-4.0.0	1.59199E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85914E-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	0.0642	likely_benign	0.0632	benign	-0.839	Destabilizing	None	N	0.296	neutral	None	None	None	None	N
S/C	0.1551	likely_benign	0.1609	benign	-0.919	Destabilizing	None	N	0.374	neutral	N	0.430836466	None	None	N
S/D	0.9351	likely_pathogenic	0.9476	pathogenic	-1.753	Destabilizing	0.002	N	0.414	neutral	None	None	None	None	N
S/E	0.9231	likely_pathogenic	0.9342	pathogenic	-1.614	Destabilizing	0.002	N	0.428	neutral	None	None	None	None	N
S/F	0.8933	likely_pathogenic	0.9064	pathogenic	-0.756	Destabilizing	0.018	N	0.591	neutral	None	None	None	None	N
S/G	0.027	likely_benign	0.0283	benign	-1.177	Destabilizing	None	N	0.337	neutral	N	0.387296333	None	None	N
S/H	0.9333	likely_pathogenic	0.9434	pathogenic	-1.563	Destabilizing	0.116	N	0.663	neutral	None	None	None	None	N
S/I	0.4564	ambiguous	0.4981	ambiguous	-0.007	Destabilizing	0.001	N	0.528	neutral	N	0.428929525	None	None	N
S/K	0.983	likely_pathogenic	0.9861	pathogenic	-0.678	Destabilizing	0.002	N	0.416	neutral	None	None	None	None	N
S/L	0.5686	likely_pathogenic	0.5814	pathogenic	-0.007	Destabilizing	None	N	0.475	neutral	None	None	None	None	N
S/M	0.7116	likely_pathogenic	0.7313	pathogenic	-0.013	Destabilizing	0.116	N	0.663	neutral	None	None	None	None	N
S/N	0.7881	likely_pathogenic	0.8114	pathogenic	-1.254	Destabilizing	0.001	N	0.414	neutral	N	0.430836466	None	None	N
S/P	0.9714	likely_pathogenic	0.9799	pathogenic	-0.251	Destabilizing	0.003	N	0.475	neutral	None	None	None	None	N
S/Q	0.9239	likely_pathogenic	0.9313	pathogenic	-1.172	Destabilizing	0.008	N	0.476	neutral	None	None	None	None	N
S/R	0.9541	likely_pathogenic	0.9614	pathogenic	-0.838	Destabilizing	0.006	N	0.478	neutral	N	0.430836466	None	None	N
S/T	0.2453	likely_benign	0.2594	benign	-0.936	Destabilizing	0.001	N	0.364	neutral	N	0.430316392	None	None	N
S/V	0.3537	ambiguous	0.3991	ambiguous	-0.251	Destabilizing	None	N	0.476	neutral	None	None	None	None	N
S/W	0.9258	likely_pathogenic	0.9406	pathogenic	-0.969	Destabilizing	0.316	N	0.745	deleterious	None	None	None	None	N
S/Y	0.8427	likely_pathogenic	0.8753	pathogenic	-0.561	Destabilizing	0.051	N	0.631	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.