TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	14089	42490;42491;42492	chr2:178634516;178634515;178634514	chr2:179499243;179499242;179499241
N2AB	12448	37567;37568;37569	chr2:178634516;178634515;178634514	chr2:179499243;179499242;179499241
N2A	11521	34786;34787;34788	chr2:178634516;178634515;178634514	chr2:179499243;179499242;179499241
N2B	5024	15295;15296;15297	chr2:178634516;178634515;178634514	chr2:179499243;179499242;179499241
Novex-1	5149	15670;15671;15672	chr2:178634516;178634515;178634514	chr2:179499243;179499242;179499241
Novex-2	5216	15871;15872;15873	chr2:178634516;178634515;178634514	chr2:179499243;179499242;179499241
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCT
• RefSeq wild type template codon: GGA
• Domain: Ig-91
• Domain position: 36
• Structural Position: 52
• Q(SASA): 0.9393
• Predicted PPI site: I

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
P/H	rs201340186	0.057	0.693	N	0.301	0.137	None	gnomAD-2.1.1	2.86E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	1.59898E-04	2.35E-05	1.40687E-04
P/H	rs201340186	0.057	0.693	N	0.301	0.137	None	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	0	0	0	0	0	None	1.89143E-04	0	0	0	0
P/H	rs201340186	0.057	0.693	N	0.301	0.137	None	gnomAD-4.0.0	8.97489E-06	None	None	None	None	I	None	0	0	None	0	0	None	6.28062E-05	0	4.7892E-06	0	2.84689E-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
P/A	0.0897	likely_benign	0.075	benign	-0.299	Destabilizing	0.001	N	0.117	neutral	N	0.382581408	None	None	I
P/C	0.6177	likely_pathogenic	0.5474	ambiguous	-0.781	Destabilizing	0.901	D	0.308	neutral	None	None	None	None	I
P/D	0.3027	likely_benign	0.2582	benign	-0.299	Destabilizing	0.001	N	0.152	neutral	None	None	None	None	I
P/E	0.2372	likely_benign	0.2007	benign	-0.42	Destabilizing	0.08	N	0.274	neutral	None	None	None	None	I
P/F	0.6323	likely_pathogenic	0.541	ambiguous	-0.711	Destabilizing	0.596	D	0.381	neutral	None	None	None	None	I
P/G	0.2974	likely_benign	0.2503	benign	-0.345	Destabilizing	0.036	N	0.258	neutral	None	None	None	None	I
P/H	0.2252	likely_benign	0.1815	benign	0.013	Stabilizing	0.693	D	0.301	neutral	N	0.412075947	None	None	I
P/I	0.4059	ambiguous	0.3146	benign	-0.322	Destabilizing	0.174	N	0.335	neutral	None	None	None	None	I
P/K	0.2514	likely_benign	0.2062	benign	-0.329	Destabilizing	0.08	N	0.281	neutral	None	None	None	None	I
P/L	0.1768	likely_benign	0.1413	benign	-0.322	Destabilizing	None	N	0.189	neutral	N	0.437153568	None	None	I
P/M	0.3424	ambiguous	0.2737	benign	-0.524	Destabilizing	0.596	D	0.301	neutral	None	None	None	None	I
P/N	0.2471	likely_benign	0.2019	benign	-0.131	Destabilizing	0.002	N	0.171	neutral	None	None	None	None	I
P/Q	0.166	likely_benign	0.1377	benign	-0.345	Destabilizing	0.296	N	0.345	neutral	None	None	None	None	I
P/R	0.2047	likely_benign	0.1746	benign	0.104	Stabilizing	0.241	N	0.355	neutral	N	0.378513747	None	None	I
P/S	0.1159	likely_benign	0.0977	benign	-0.44	Destabilizing	0.001	N	0.115	neutral	N	0.338927173	None	None	I
P/T	0.0904	likely_benign	0.0748	benign	-0.472	Destabilizing	None	N	0.115	neutral	N	0.386192754	None	None	I
P/V	0.2943	likely_benign	0.2289	benign	-0.287	Destabilizing	0.08	N	0.239	neutral	None	None	None	None	I
P/W	0.749	likely_pathogenic	0.6954	pathogenic	-0.764	Destabilizing	0.972	D	0.299	neutral	None	None	None	None	I
P/Y	0.5765	likely_pathogenic	0.486	ambiguous	-0.489	Destabilizing	0.749	D	0.365	neutral	None	None	None	None	I

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.