TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5085	15478;15479;15480	chr2:178734571;178734570;178734569	chr2:179599298;179599297;179599296
N2AB	4768	14527;14528;14529	chr2:178734571;178734570;178734569	chr2:179599298;179599297;179599296
N2A	3841	11746;11747;11748	chr2:178734571;178734570;178734569	chr2:179599298;179599297;179599296
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAC
• RefSeq wild type template codon: CTG
• Domain: Ig-34
• Domain position: 11
• Structural Position: 14
• Q(SASA): 0.8712
• 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
D/G	None	None	0.324	N	0.346	0.293	0.253205268125	gnomAD-4.0.0	1.3937E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.82085E-06	0	0
D/N	rs374299783	0.406	0.324	N	0.342	0.108	None	gnomAD-2.1.1	8.76E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	1.9E-05	0
D/N	rs374299783	0.406	0.324	N	0.342	0.108	None	gnomAD-3.1.2	4.6E-05	None	None	None	None	I	None	2.41E-05	0	0	0	0	None	0	0	8.82E-05	0	0
D/N	rs374299783	0.406	0.324	N	0.342	0.108	None	gnomAD-4.0.0	5.29193E-05	None	None	None	None	I	None	1.35168E-05	0	None	0	0	None	0	0	6.94455E-05	0	3.26115E-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
D/A	0.1867	likely_benign	0.1405	benign	-0.052	Destabilizing	0.09	N	0.353	neutral	N	0.483582931	None	None	I
D/C	0.7041	likely_pathogenic	0.5973	pathogenic	-0.103	Destabilizing	0.981	D	0.435	neutral	None	None	None	None	I
D/E	0.1627	likely_benign	0.1237	benign	-0.301	Destabilizing	None	N	0.149	neutral	N	0.363555349	None	None	I
D/F	0.6185	likely_pathogenic	0.5159	ambiguous	-0.039	Destabilizing	0.818	D	0.424	neutral	None	None	None	None	I
D/G	0.2272	likely_benign	0.1693	benign	-0.205	Destabilizing	0.324	N	0.346	neutral	N	0.484154861	None	None	I
D/H	0.3271	likely_benign	0.2654	benign	0.443	Stabilizing	0.001	N	0.248	neutral	N	0.500274243	None	None	I
D/I	0.4197	ambiguous	0.2938	benign	0.292	Stabilizing	0.818	D	0.427	neutral	None	None	None	None	I
D/K	0.5045	ambiguous	0.3474	ambiguous	0.417	Stabilizing	0.241	N	0.339	neutral	None	None	None	None	I
D/L	0.434	ambiguous	0.3405	ambiguous	0.292	Stabilizing	0.388	N	0.441	neutral	None	None	None	None	I
D/M	0.6485	likely_pathogenic	0.523	ambiguous	0.143	Stabilizing	0.981	D	0.402	neutral	None	None	None	None	I
D/N	0.1001	likely_benign	0.087	benign	0.091	Stabilizing	0.324	N	0.342	neutral	N	0.484814305	None	None	I
D/P	0.7607	likely_pathogenic	0.6374	pathogenic	0.199	Stabilizing	0.818	D	0.385	neutral	None	None	None	None	I
D/Q	0.3942	ambiguous	0.2884	benign	0.116	Stabilizing	0.241	N	0.301	neutral	None	None	None	None	I
D/R	0.5332	ambiguous	0.3843	ambiguous	0.665	Stabilizing	0.388	N	0.416	neutral	None	None	None	None	I
D/S	0.1367	likely_benign	0.1085	benign	0.012	Stabilizing	0.116	N	0.295	neutral	None	None	None	None	I
D/T	0.2856	likely_benign	0.1987	benign	0.137	Stabilizing	0.388	N	0.364	neutral	None	None	None	None	I
D/V	0.2384	likely_benign	0.1671	benign	0.199	Stabilizing	0.324	N	0.443	neutral	N	0.460146082	None	None	I
D/W	0.9178	likely_pathogenic	0.8648	pathogenic	0.042	Stabilizing	0.981	D	0.499	neutral	None	None	None	None	I
D/Y	0.2676	likely_benign	0.2121	benign	0.195	Stabilizing	0.457	N	0.434	neutral	N	0.498357913	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.