TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35347	106264;106265;106266	chr2:178530576;178530575;178530574	chr2:179395303;179395302;179395301
N2AB	33706	101341;101342;101343	chr2:178530576;178530575;178530574	chr2:179395303;179395302;179395301
N2A	32779	98560;98561;98562	chr2:178530576;178530575;178530574	chr2:179395303;179395302;179395301
N2B	26282	79069;79070;79071	chr2:178530576;178530575;178530574	chr2:179395303;179395302;179395301
Novex-1	26407	79444;79445;79446	chr2:178530576;178530575;178530574	chr2:179395303;179395302;179395301
Novex-2	26474	79645;79646;79647	chr2:178530576;178530575;178530574	chr2:179395303;179395302;179395301
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Ig-165
• Domain position: 62
• Structural Position: 141
• Q(SASA): 0.3345
• 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
N/S	rs769505255	-1.14	None	N	0.089	0.085	0.101711395817	gnomAD-2.1.1	1.2E-05	None	None	None	None	N	None	0	0	None	0	0	None	9.8E-05	None	0	0	0
N/S	rs769505255	-1.14	None	N	0.089	0.085	0.101711395817	gnomAD-4.0.0	4.78895E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99391E-07	6.95604E-05	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
N/A	0.2176	likely_benign	0.2154	benign	-0.796	Destabilizing	0.002	N	0.336	neutral	None	None	None	None	N
N/C	0.157	likely_benign	0.1578	benign	-0.039	Destabilizing	0.497	N	0.497	neutral	None	None	None	None	N
N/D	0.144	likely_benign	0.1394	benign	-1.231	Destabilizing	0.006	N	0.257	neutral	N	0.439223876	None	None	N
N/E	0.2548	likely_benign	0.2365	benign	-1.083	Destabilizing	0.004	N	0.225	neutral	None	None	None	None	N
N/F	0.3225	likely_benign	0.337	benign	-0.384	Destabilizing	0.009	N	0.477	neutral	None	None	None	None	N
N/G	0.2689	likely_benign	0.2675	benign	-1.186	Destabilizing	0.008	N	0.219	neutral	None	None	None	None	N
N/H	0.0499	likely_benign	0.0494	benign	-0.951	Destabilizing	None	N	0.09	neutral	N	0.416368446	None	None	N
N/I	0.1451	likely_benign	0.1508	benign	0.219	Stabilizing	0.007	N	0.471	neutral	N	0.458292427	None	None	N
N/K	0.19	likely_benign	0.1838	benign	-0.428	Destabilizing	0.003	N	0.223	neutral	N	0.434759419	None	None	N
N/L	0.1245	likely_benign	0.1254	benign	0.219	Stabilizing	None	N	0.187	neutral	None	None	None	None	N
N/M	0.3064	likely_benign	0.317	benign	0.689	Stabilizing	0.074	N	0.512	neutral	None	None	None	None	N
N/P	0.5379	ambiguous	0.4946	ambiguous	-0.089	Destabilizing	0.085	N	0.499	neutral	None	None	None	None	N
N/Q	0.1787	likely_benign	0.1734	benign	-1.048	Destabilizing	None	N	0.094	neutral	None	None	None	None	N
N/R	0.1606	likely_benign	0.1559	benign	-0.563	Destabilizing	0.009	N	0.271	neutral	None	None	None	None	N
N/S	0.1093	likely_benign	0.1109	benign	-1.131	Destabilizing	None	N	0.089	neutral	N	0.40208964	None	None	N
N/T	0.1222	likely_benign	0.1218	benign	-0.793	Destabilizing	0.003	N	0.229	neutral	N	0.416675091	None	None	N
N/V	0.1933	likely_benign	0.197	benign	-0.089	Destabilizing	0.009	N	0.456	neutral	None	None	None	None	N
N/W	0.5503	ambiguous	0.5445	ambiguous	-0.229	Destabilizing	0.245	N	0.495	neutral	None	None	None	None	N
N/Y	0.0891	likely_benign	0.0903	benign	0.026	Stabilizing	None	N	0.146	neutral	N	0.480841212	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.