TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30537	91834;91835;91836	chr2:178550229;178550228;178550227	chr2:179414956;179414955;179414954
N2AB	28896	86911;86912;86913	chr2:178550229;178550228;178550227	chr2:179414956;179414955;179414954
N2A	27969	84130;84131;84132	chr2:178550229;178550228;178550227	chr2:179414956;179414955;179414954
N2B	21472	64639;64640;64641	chr2:178550229;178550228;178550227	chr2:179414956;179414955;179414954
Novex-1	21597	65014;65015;65016	chr2:178550229;178550228;178550227	chr2:179414956;179414955;179414954
Novex-2	21664	65215;65216;65217	chr2:178550229;178550228;178550227	chr2:179414956;179414955;179414954
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-149
• Domain position: 6
• Structural Position: 14
• Q(SASA): 0.5376
• 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
I/N	None	None	None	N	0.209	0.274	0.232513804876	gnomAD-4.0.0	6.84354E-07	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99604E-07	0	0
I/S	rs758126299	-0.924	0.012	N	0.26	0.183	0.232513804876	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
I/S	rs758126299	-0.924	0.012	N	0.26	0.183	0.232513804876	gnomAD-4.0.0	2.73742E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.59842E-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
I/A	0.1583	likely_benign	0.1828	benign	-1.062	Destabilizing	0.007	N	0.187	neutral	None	None	None	None	N
I/C	0.4142	ambiguous	0.4433	ambiguous	-0.859	Destabilizing	0.356	N	0.312	neutral	None	None	None	None	N
I/D	0.3412	ambiguous	0.4141	ambiguous	-0.457	Destabilizing	0.038	N	0.349	neutral	None	None	None	None	N
I/E	0.2692	likely_benign	0.3066	benign	-0.488	Destabilizing	0.072	N	0.35	neutral	None	None	None	None	N
I/F	0.1197	likely_benign	0.144	benign	-0.68	Destabilizing	0.055	N	0.264	neutral	N	0.493023391	None	None	N
I/G	0.365	ambiguous	0.4453	ambiguous	-1.316	Destabilizing	0.031	N	0.296	neutral	None	None	None	None	N
I/H	0.2449	likely_benign	0.2717	benign	-0.43	Destabilizing	0.356	N	0.307	neutral	None	None	None	None	N
I/K	0.2155	likely_benign	0.2442	benign	-0.781	Destabilizing	0.072	N	0.347	neutral	None	None	None	None	N
I/L	0.0839	likely_benign	0.0874	benign	-0.472	Destabilizing	0.005	N	0.154	neutral	N	0.48230265	None	None	N
I/M	0.0808	likely_benign	0.0881	benign	-0.546	Destabilizing	0.171	N	0.267	neutral	D	0.524573347	None	None	N
I/N	0.1044	likely_benign	0.1192	benign	-0.655	Destabilizing	None	N	0.209	neutral	N	0.483615641	None	None	N
I/P	0.4949	ambiguous	0.5973	pathogenic	-0.636	Destabilizing	0.136	N	0.409	neutral	None	None	None	None	N
I/Q	0.2153	likely_benign	0.2304	benign	-0.822	Destabilizing	0.356	N	0.41	neutral	None	None	None	None	N
I/R	0.181	likely_benign	0.2151	benign	-0.195	Destabilizing	0.072	N	0.414	neutral	None	None	None	None	N
I/S	0.1247	likely_benign	0.1369	benign	-1.196	Destabilizing	0.012	N	0.26	neutral	N	0.514566997	None	None	N
I/T	0.0798	likely_benign	0.0833	benign	-1.112	Destabilizing	None	N	0.121	neutral	N	0.463503458	None	None	N
I/V	0.0586	likely_benign	0.0617	benign	-0.636	Destabilizing	None	N	0.151	neutral	N	0.483916016	None	None	N
I/W	0.6173	likely_pathogenic	0.678	pathogenic	-0.711	Destabilizing	0.864	D	0.298	neutral	None	None	None	None	N
I/Y	0.3264	likely_benign	0.3614	ambiguous	-0.495	Destabilizing	0.356	N	0.372	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.