TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	34391	103396;103397;103398	chr2:178533444;178533443;178533442	chr2:179398171;179398170;179398169
N2AB	32750	98473;98474;98475	chr2:178533444;178533443;178533442	chr2:179398171;179398170;179398169
N2A	31823	95692;95693;95694	chr2:178533444;178533443;178533442	chr2:179398171;179398170;179398169
N2B	25326	76201;76202;76203	chr2:178533444;178533443;178533442	chr2:179398171;179398170;179398169
Novex-1	25451	76576;76577;76578	chr2:178533444;178533443;178533442	chr2:179398171;179398170;179398169
Novex-2	25518	76777;76778;76779	chr2:178533444;178533443;178533442	chr2:179398171;179398170;179398169
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Ig-162
• Domain position: 29
• Structural Position: 43
• Q(SASA): 0.4369
• 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/L	rs775343253	-0.398	0.012	N	0.437	0.148	0.30212335484	gnomAD-2.1.1	7.14E-06	None	None	None	None	I	None	4.14E-05	0	None	0	0	None	0	None	0	7.81E-06	0
P/L	rs775343253	-0.398	0.012	N	0.437	0.148	0.30212335484	gnomAD-3.1.2	1.31E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	1.47E-05	0	0
P/L	rs775343253	-0.398	0.012	N	0.437	0.148	0.30212335484	gnomAD-4.0.0	2.04512E-05	None	None	None	None	I	None	1.33511E-05	0	None	0	0	None	1.56465E-05	0	2.62755E-05	0	0
P/Q	None	-0.608	0.055	N	0.457	0.105	0.152612264143	gnomAD-2.1.1	4.02E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	0	0
P/Q	None	-0.608	0.055	N	0.457	0.105	0.152612264143	gnomAD-4.0.0	1.36848E-06	None	None	None	None	I	None	0	4.47227E-05	None	0	0	None	0	0	0	0	0
P/R	rs775343253	-0.062	None	N	0.217	0.169	0.171388866994	gnomAD-2.1.1	8.05E-06	None	None	None	None	I	None	0	2.9E-05	None	0	0	None	0	None	0	8.88E-06	0
P/R	rs775343253	-0.062	None	N	0.217	0.169	0.171388866994	gnomAD-4.0.0	2.73696E-06	None	None	None	None	I	None	0	2.23614E-05	None	0	0	None	0	0	2.69834E-06	0	0
P/S	None	None	None	N	0.155	0.087	0.117506650769	gnomAD-4.0.0	6.36503E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.57407E-06	0	3.02407E-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	0.0753	likely_benign	0.0596	benign	-0.47	Destabilizing	None	N	0.169	neutral	N	0.456001483	None	None	I
P/C	0.5917	likely_pathogenic	0.4022	ambiguous	-0.523	Destabilizing	0.356	N	0.551	neutral	None	None	None	None	I
P/D	0.607	likely_pathogenic	0.3853	ambiguous	-0.479	Destabilizing	0.031	N	0.383	neutral	None	None	None	None	I
P/E	0.3345	likely_benign	0.2115	benign	-0.603	Destabilizing	0.016	N	0.381	neutral	None	None	None	None	I
P/F	0.5643	likely_pathogenic	0.3475	ambiguous	-0.757	Destabilizing	0.356	N	0.572	neutral	None	None	None	None	I
P/G	0.4859	ambiguous	0.3033	benign	-0.591	Destabilizing	0.007	N	0.397	neutral	None	None	None	None	I
P/H	0.2553	likely_benign	0.1451	benign	-0.189	Destabilizing	0.356	N	0.547	neutral	None	None	None	None	I
P/I	0.2822	likely_benign	0.1795	benign	-0.301	Destabilizing	0.072	N	0.545	neutral	None	None	None	None	I
P/K	0.286	likely_benign	0.1583	benign	-0.468	Destabilizing	None	N	0.155	neutral	None	None	None	None	I
P/L	0.1284	likely_benign	0.0803	benign	-0.301	Destabilizing	0.012	N	0.437	neutral	N	0.447536715	None	None	I
P/M	0.306	likely_benign	0.1902	benign	-0.327	Destabilizing	0.356	N	0.548	neutral	None	None	None	None	I
P/N	0.4247	ambiguous	0.2496	benign	-0.142	Destabilizing	0.016	N	0.443	neutral	None	None	None	None	I
P/Q	0.1699	likely_benign	0.1019	benign	-0.417	Destabilizing	0.055	N	0.457	neutral	N	0.459540433	None	None	I
P/R	0.2216	likely_benign	0.1317	benign	0.088	Stabilizing	None	N	0.217	neutral	N	0.435415567	None	None	I
P/S	0.1442	likely_benign	0.0974	benign	-0.454	Destabilizing	None	N	0.155	neutral	N	0.47529932	None	None	I
P/T	0.1198	likely_benign	0.0817	benign	-0.484	Destabilizing	None	N	0.159	neutral	N	0.429622958	None	None	I
P/V	0.1941	likely_benign	0.13	benign	-0.323	Destabilizing	0.016	N	0.459	neutral	None	None	None	None	I
P/W	0.7998	likely_pathogenic	0.595	pathogenic	-0.836	Destabilizing	0.864	D	0.553	neutral	None	None	None	None	I
P/Y	0.5348	ambiguous	0.3491	ambiguous	-0.541	Destabilizing	0.356	N	0.577	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.