TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30211	90856;90857;90858	chr2:178552269;178552268;178552267	chr2:179416996;179416995;179416994
N2AB	28570	85933;85934;85935	chr2:178552269;178552268;178552267	chr2:179416996;179416995;179416994
N2A	27643	83152;83153;83154	chr2:178552269;178552268;178552267	chr2:179416996;179416995;179416994
N2B	21146	63661;63662;63663	chr2:178552269;178552268;178552267	chr2:179416996;179416995;179416994
Novex-1	21271	64036;64037;64038	chr2:178552269;178552268;178552267	chr2:179416996;179416995;179416994
Novex-2	21338	64237;64238;64239	chr2:178552269;178552268;178552267	chr2:179416996;179416995;179416994
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGT
• RefSeq wild type template codon: ACA
• Domain: Ig-148
• Domain position: 80
• Structural Position: 164
• Q(SASA): 0.262
• 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
C/R	rs1329290797	0.077	0.241	N	0.479	0.207	0.399889258716	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.92E-06	0
C/R	rs1329290797	0.077	0.241	N	0.479	0.207	0.399889258716	gnomAD-4.0.0	1.59183E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	2.85889E-06	0	0
C/Y	None	None	0.061	N	0.425	0.216	0.400033932507	gnomAD-4.0.0	2.73727E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	3.59817E-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
C/A	0.3417	ambiguous	0.308	benign	-0.827	Destabilizing	0.001	N	0.079	neutral	None	None	None	None	I
C/D	0.7536	likely_pathogenic	0.6344	pathogenic	0.32	Stabilizing	0.148	N	0.406	neutral	None	None	None	None	I
C/E	0.8318	likely_pathogenic	0.7669	pathogenic	0.294	Stabilizing	0.148	N	0.358	neutral	None	None	None	None	I
C/F	0.3392	likely_benign	0.2781	benign	-0.713	Destabilizing	0.061	N	0.429	neutral	N	0.438102716	None	None	I
C/G	0.1588	likely_benign	0.1317	benign	-0.982	Destabilizing	0.028	N	0.318	neutral	N	0.225447217	None	None	I
C/H	0.5259	ambiguous	0.4169	ambiguous	-0.916	Destabilizing	0.001	N	0.245	neutral	None	None	None	None	I
C/I	0.665	likely_pathogenic	0.6482	pathogenic	-0.498	Destabilizing	0.001	N	0.157	neutral	None	None	None	None	I
C/K	0.7746	likely_pathogenic	0.6991	pathogenic	-0.157	Destabilizing	0.08	N	0.361	neutral	None	None	None	None	I
C/L	0.5616	ambiguous	0.5521	ambiguous	-0.498	Destabilizing	0.016	N	0.271	neutral	None	None	None	None	I
C/M	0.6364	likely_pathogenic	0.6362	pathogenic	-0.013	Destabilizing	0.749	D	0.339	neutral	None	None	None	None	I
C/N	0.4182	ambiguous	0.3341	benign	0.184	Stabilizing	0.08	N	0.407	neutral	None	None	None	None	I
C/P	0.9821	likely_pathogenic	0.9772	pathogenic	-0.584	Destabilizing	0.46	N	0.479	neutral	None	None	None	None	I
C/Q	0.6023	likely_pathogenic	0.5194	ambiguous	0.034	Stabilizing	0.296	N	0.461	neutral	None	None	None	None	I
C/R	0.539	ambiguous	0.4253	ambiguous	0.203	Stabilizing	0.241	N	0.479	neutral	N	0.389367406	None	None	I
C/S	0.2011	likely_benign	0.162	benign	-0.301	Destabilizing	0.001	N	0.153	neutral	N	0.34925158	None	None	I
C/T	0.3781	ambiguous	0.3333	benign	-0.2	Destabilizing	0.036	N	0.279	neutral	None	None	None	None	I
C/V	0.5075	ambiguous	0.5098	ambiguous	-0.584	Destabilizing	0.001	N	0.145	neutral	None	None	None	None	I
C/W	0.7219	likely_pathogenic	0.6457	pathogenic	-0.655	Destabilizing	0.001	N	0.22	neutral	N	0.4086466	None	None	I
C/Y	0.4007	ambiguous	0.3141	benign	-0.562	Destabilizing	0.061	N	0.425	neutral	N	0.437929357	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.