TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27126	81601;81602;81603	chr2:178564756;178564755;178564754	chr2:179429483;179429482;179429481
N2AB	25485	76678;76679;76680	chr2:178564756;178564755;178564754	chr2:179429483;179429482;179429481
N2A	24558	73897;73898;73899	chr2:178564756;178564755;178564754	chr2:179429483;179429482;179429481
N2B	18061	54406;54407;54408	chr2:178564756;178564755;178564754	chr2:179429483;179429482;179429481
Novex-1	18186	54781;54782;54783	chr2:178564756;178564755;178564754	chr2:179429483;179429482;179429481
Novex-2	18253	54982;54983;54984	chr2:178564756;178564755;178564754	chr2:179429483;179429482;179429481
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCC
• RefSeq wild type template codon: GGG
• Domain: Fn3-85
• Domain position: 55
• Structural Position: 75
• Q(SASA): 0.3965
• 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
P/A	None	None	0.001	N	0.161	0.132	0.211220785272	gnomAD-4.0.0	1.59452E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86302E-06	0	0
P/T	None	None	0.183	N	0.379	0.091	0.243398259712	gnomAD-4.0.0	1.59452E-06	None	None	None	None	N	None	0	0	None	0	2.78831E-05	None	0	0	0	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
P/A	0.0778	likely_benign	0.0781	benign	-1.479	Destabilizing	0.001	N	0.161	neutral	N	0.517825441	None	None	N
P/C	0.3135	likely_benign	0.3195	benign	-0.826	Destabilizing	0.836	D	0.422	neutral	None	None	None	None	N
P/D	0.7631	likely_pathogenic	0.78	pathogenic	-1.727	Destabilizing	0.593	D	0.416	neutral	None	None	None	None	N
P/E	0.4816	ambiguous	0.4913	ambiguous	-1.765	Destabilizing	0.418	N	0.362	neutral	None	None	None	None	N
P/F	0.4272	ambiguous	0.4396	ambiguous	-1.286	Destabilizing	0.264	N	0.486	neutral	None	None	None	None	N
P/G	0.395	ambiguous	0.4105	ambiguous	-1.759	Destabilizing	0.264	N	0.414	neutral	None	None	None	None	N
P/H	0.2898	likely_benign	0.2994	benign	-1.397	Destabilizing	0.921	D	0.377	neutral	N	0.49708359	None	None	N
P/I	0.1125	likely_benign	0.1052	benign	-0.814	Destabilizing	0.004	N	0.354	neutral	None	None	None	None	N
P/K	0.3331	likely_benign	0.3494	ambiguous	-1.273	Destabilizing	0.418	N	0.382	neutral	None	None	None	None	N
P/L	0.0552	likely_benign	0.0531	benign	-0.814	Destabilizing	None	N	0.31	neutral	N	0.437345859	None	None	N
P/M	0.1709	likely_benign	0.1717	benign	-0.462	Destabilizing	0.716	D	0.432	neutral	None	None	None	None	N
P/N	0.4282	ambiguous	0.4504	ambiguous	-0.98	Destabilizing	0.836	D	0.444	neutral	None	None	None	None	N
P/Q	0.2058	likely_benign	0.2122	benign	-1.229	Destabilizing	0.836	D	0.413	neutral	None	None	None	None	N
P/R	0.2278	likely_benign	0.2379	benign	-0.674	Destabilizing	0.794	D	0.458	neutral	N	0.472099119	None	None	N
P/S	0.1864	likely_benign	0.1957	benign	-1.38	Destabilizing	0.101	N	0.391	neutral	N	0.515843928	None	None	N
P/T	0.1098	likely_benign	0.1096	benign	-1.327	Destabilizing	0.183	N	0.379	neutral	N	0.506091082	None	None	N
P/V	0.0866	likely_benign	0.083	benign	-1.003	Destabilizing	0.061	N	0.331	neutral	None	None	None	None	N
P/W	0.6015	likely_pathogenic	0.6091	pathogenic	-1.481	Destabilizing	0.983	D	0.448	neutral	None	None	None	None	N
P/Y	0.4491	ambiguous	0.4598	ambiguous	-1.22	Destabilizing	0.836	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.