TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4682	14269;14270;14271	chr2:178739189;178739188;178739187	chr2:179603916;179603915;179603914
N2AB	4365	13318;13319;13320	chr2:178739189;178739188;178739187	chr2:179603916;179603915;179603914
N2A	None	None	chr2:None	chr2:None
N2B	4319	13180;13181;13182	chr2:178739189;178739188;178739187	chr2:179603916;179603915;179603914
Novex-1	4444	13555;13556;13557	chr2:178739189;178739188;178739187	chr2:179603916;179603915;179603914
Novex-2	4511	13756;13757;13758	chr2:178739189;178739188;178739187	chr2:179603916;179603915;179603914
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-29
• Domain position: 77
• Structural Position: 162
• Q(SASA): 1.1175
• 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
D/G	rs2082045865	None	None	N	0.147	0.155	None	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
D/G	rs2082045865	None	None	N	0.147	0.155	None	gnomAD-4.0.0	2.91265E-06	None	None	None	None	N	None	1.78171E-05	0	None	0	2.48373E-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
D/A	0.117	likely_benign	0.115	benign	0.059	Stabilizing	None	N	0.143	neutral	N	0.489508503	None	None	N
D/C	0.4189	ambiguous	0.4085	ambiguous	0.066	Stabilizing	0.676	D	0.209	neutral	None	None	None	None	N
D/E	0.1295	likely_benign	0.1285	benign	-0.26	Destabilizing	None	N	0.135	neutral	N	0.439011221	None	None	N
D/F	0.4019	ambiguous	0.4009	ambiguous	-0.144	Destabilizing	None	N	0.251	neutral	None	None	None	None	N
D/G	0.1062	likely_benign	0.1119	benign	-0.031	Destabilizing	None	N	0.147	neutral	N	0.497144159	None	None	N
D/H	0.164	likely_benign	0.1603	benign	0.366	Stabilizing	0.295	N	0.271	neutral	D	0.607985997	None	None	N
D/I	0.2175	likely_benign	0.2149	benign	0.224	Stabilizing	0.072	N	0.249	neutral	None	None	None	None	N
D/K	0.1672	likely_benign	0.169	benign	0.512	Stabilizing	0.016	N	0.247	neutral	None	None	None	None	N
D/L	0.2531	likely_benign	0.2534	benign	0.224	Stabilizing	0.016	N	0.229	neutral	None	None	None	None	N
D/M	0.4602	ambiguous	0.4699	ambiguous	0.139	Stabilizing	0.356	N	0.219	neutral	None	None	None	None	N
D/N	0.0915	likely_benign	0.0935	benign	0.407	Stabilizing	0.055	N	0.278	neutral	N	0.504674529	None	None	N
D/P	0.4787	ambiguous	0.4706	ambiguous	0.187	Stabilizing	0.072	N	0.324	neutral	None	None	None	None	N
D/Q	0.1983	likely_benign	0.2007	benign	0.386	Stabilizing	0.001	N	0.226	neutral	None	None	None	None	N
D/R	0.1883	likely_benign	0.1908	benign	0.635	Stabilizing	0.038	N	0.309	neutral	None	None	None	None	N
D/S	0.0947	likely_benign	0.0995	benign	0.294	Stabilizing	0.016	N	0.22	neutral	None	None	None	None	N
D/T	0.1616	likely_benign	0.1633	benign	0.367	Stabilizing	0.016	N	0.262	neutral	None	None	None	None	N
D/V	0.1441	likely_benign	0.1386	benign	0.187	Stabilizing	0.029	N	0.265	neutral	N	0.511143612	None	None	N
D/W	0.7448	likely_pathogenic	0.7406	pathogenic	-0.144	Destabilizing	0.864	D	0.215	neutral	None	None	None	None	N
D/Y	0.1596	likely_benign	0.1501	benign	0.072	Stabilizing	0.093	N	0.276	neutral	N	0.507405094	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.