TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31001	93226;93227;93228	chr2:178548625;178548624;178548623	chr2:179413352;179413351;179413350
N2AB	29360	88303;88304;88305	chr2:178548625;178548624;178548623	chr2:179413352;179413351;179413350
N2A	28433	85522;85523;85524	chr2:178548625;178548624;178548623	chr2:179413352;179413351;179413350
N2B	21936	66031;66032;66033	chr2:178548625;178548624;178548623	chr2:179413352;179413351;179413350
Novex-1	22061	66406;66407;66408	chr2:178548625;178548624;178548623	chr2:179413352;179413351;179413350
Novex-2	22128	66607;66608;66609	chr2:178548625;178548624;178548623	chr2:179413352;179413351;179413350
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAC
• RefSeq wild type template codon: TTG
• Domain: Ig-150
• Domain position: 75
• Structural Position: 162
• Q(SASA): 0.9945
• 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
N/D	None	None	0.928	N	0.447	0.237	0.195762928549	gnomAD-4.0.0	1.20032E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.3125E-06	0	0
N/S	rs1308531791	0.342	0.146	N	0.414	0.068	0.0846915920261	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.91E-06	0
N/S	rs1308531791	0.342	0.146	N	0.414	0.068	0.0846915920261	gnomAD-4.0.0	6.15761E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.095E-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
N/A	0.1233	likely_benign	0.1156	benign	-0.167	Destabilizing	0.895	D	0.438	neutral	None	None	None	None	I
N/C	0.1729	likely_benign	0.1607	benign	0.227	Stabilizing	0.999	D	0.713	prob.delet.	None	None	None	None	I
N/D	0.1121	likely_benign	0.111	benign	-0.006	Destabilizing	0.928	D	0.447	neutral	N	0.430143033	None	None	I
N/E	0.2586	likely_benign	0.2563	benign	-0.078	Destabilizing	0.944	D	0.501	neutral	None	None	None	None	I
N/F	0.4002	ambiguous	0.3798	ambiguous	-0.789	Destabilizing	0.992	D	0.678	prob.neutral	None	None	None	None	I
N/G	0.1696	likely_benign	0.1608	benign	-0.243	Destabilizing	0.895	D	0.425	neutral	None	None	None	None	I
N/H	0.0972	likely_benign	0.0958	benign	-0.321	Destabilizing	0.989	D	0.621	neutral	N	0.499426973	None	None	I
N/I	0.1174	likely_benign	0.1129	benign	-0.065	Destabilizing	0.989	D	0.676	prob.neutral	N	0.472587088	None	None	I
N/K	0.2034	likely_benign	0.205	benign	0.122	Stabilizing	0.865	D	0.499	neutral	N	0.440242597	None	None	I
N/L	0.1427	likely_benign	0.1348	benign	-0.065	Destabilizing	0.983	D	0.579	neutral	None	None	None	None	I
N/M	0.235	likely_benign	0.2256	benign	0.156	Stabilizing	0.999	D	0.634	neutral	None	None	None	None	I
N/P	0.2278	likely_benign	0.2055	benign	-0.078	Destabilizing	0.992	D	0.621	neutral	None	None	None	None	I
N/Q	0.2258	likely_benign	0.2198	benign	-0.232	Destabilizing	0.983	D	0.603	neutral	None	None	None	None	I
N/R	0.2394	likely_benign	0.2328	benign	0.192	Stabilizing	0.983	D	0.603	neutral	None	None	None	None	I
N/S	0.06	likely_benign	0.0584	benign	0.016	Stabilizing	0.146	N	0.414	neutral	N	0.396238316	None	None	I
N/T	0.0801	likely_benign	0.08	benign	0.049	Stabilizing	0.865	D	0.481	neutral	N	0.428796239	None	None	I
N/V	0.1259	likely_benign	0.1188	benign	-0.078	Destabilizing	0.983	D	0.651	neutral	None	None	None	None	I
N/W	0.7154	likely_pathogenic	0.6859	pathogenic	-0.914	Destabilizing	0.999	D	0.749	deleterious	None	None	None	None	I
N/Y	0.1581	likely_benign	0.1515	benign	-0.598	Destabilizing	0.996	D	0.643	neutral	D	0.528787088	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.