TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	4836	14731;14732;14733	chr2:178735940;178735939;178735938	chr2:179600667;179600666;179600665
N2AB	4519	13780;13781;13782	chr2:178735940;178735939;178735938	chr2:179600667;179600666;179600665
N2A	3592	10999;11000;11001	chr2:178735940;178735939;178735938	chr2:179600667;179600666;179600665
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: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Ig-31
• Domain position: 42
• Structural Position: 59
• Q(SASA): 0.5651
• 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
S/P	None	None	0.003	N	0.3	0.126	0.143124449307	gnomAD-4.0.0	1.59116E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85811E-06	0	0
S/T	None	None	0.505	N	0.443	0.091	0.171388866994	gnomAD-4.0.0	1.59116E-06	None	None	None	None	N	None	0	0	None	0	0	None	1.88246E-05	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
S/A	0.0789	likely_benign	0.0738	benign	-0.261	Destabilizing	0.174	N	0.449	neutral	N	0.50900548	None	None	N
S/C	0.1255	likely_benign	0.106	benign	-0.52	Destabilizing	0.991	D	0.543	neutral	None	None	None	None	N
S/D	0.3422	ambiguous	0.2898	benign	0.24	Stabilizing	0.575	D	0.373	neutral	None	None	None	None	N
S/E	0.3438	ambiguous	0.3092	benign	0.171	Stabilizing	0.575	D	0.376	neutral	None	None	None	None	N
S/F	0.1332	likely_benign	0.1091	benign	-1.007	Destabilizing	0.01	N	0.329	neutral	None	None	None	None	N
S/G	0.1341	likely_benign	0.1124	benign	-0.329	Destabilizing	0.575	D	0.416	neutral	None	None	None	None	N
S/H	0.2292	likely_benign	0.2009	benign	-0.492	Destabilizing	0.991	D	0.504	neutral	None	None	None	None	N
S/I	0.1194	likely_benign	0.1015	benign	-0.209	Destabilizing	0.826	D	0.575	neutral	None	None	None	None	N
S/K	0.423	ambiguous	0.3711	ambiguous	-0.257	Destabilizing	0.575	D	0.375	neutral	None	None	None	None	N
S/L	0.0763	likely_benign	0.0679	benign	-0.209	Destabilizing	0.338	N	0.511	neutral	N	0.502714098	None	None	N
S/M	0.1829	likely_benign	0.1663	benign	-0.431	Destabilizing	0.991	D	0.503	neutral	None	None	None	None	N
S/N	0.1643	likely_benign	0.1314	benign	-0.194	Destabilizing	0.906	D	0.419	neutral	None	None	None	None	N
S/P	0.0826	likely_benign	0.0892	benign	-0.201	Destabilizing	0.003	N	0.3	neutral	N	0.480271333	None	None	N
S/Q	0.3069	likely_benign	0.2855	benign	-0.306	Destabilizing	0.906	D	0.411	neutral	None	None	None	None	N
S/R	0.3865	ambiguous	0.3278	benign	-0.022	Destabilizing	0.906	D	0.478	neutral	None	None	None	None	N
S/T	0.0858	likely_benign	0.0757	benign	-0.268	Destabilizing	0.505	D	0.443	neutral	N	0.397951442	None	None	N
S/V	0.129	likely_benign	0.1133	benign	-0.201	Destabilizing	0.826	D	0.5	neutral	None	None	None	None	N
S/W	0.2342	likely_benign	0.2068	benign	-1.124	Destabilizing	0.991	D	0.673	neutral	None	None	None	None	N
S/Y	0.1295	likely_benign	0.1146	benign	-0.772	Destabilizing	0.704	D	0.579	neutral	None	None	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.