TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30549	91870;91871;91872	chr2:178550193;178550192;178550191	chr2:179414920;179414919;179414918
N2AB	28908	86947;86948;86949	chr2:178550193;178550192;178550191	chr2:179414920;179414919;179414918
N2A	27981	84166;84167;84168	chr2:178550193;178550192;178550191	chr2:179414920;179414919;179414918
N2B	21484	64675;64676;64677	chr2:178550193;178550192;178550191	chr2:179414920;179414919;179414918
Novex-1	21609	65050;65051;65052	chr2:178550193;178550192;178550191	chr2:179414920;179414919;179414918
Novex-2	21676	65251;65252;65253	chr2:178550193;178550192;178550191	chr2:179414920;179414919;179414918
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: TTG
• RefSeq wild type template codon: AAC
• Domain: Ig-149
• Domain position: 18
• Structural Position: 34
• Q(SASA): 0.8518
• 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
L/V	None	None	0.027	N	0.476	0.072	0.246773566709	gnomAD-4.0.0	1.20033E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.31251E-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
L/A	0.1279	likely_benign	0.1333	benign	-0.345	Destabilizing	0.001	N	0.243	neutral	None	None	None	None	I
L/C	0.4286	ambiguous	0.4363	ambiguous	-0.621	Destabilizing	0.824	D	0.537	neutral	None	None	None	None	I
L/D	0.4806	ambiguous	0.5035	ambiguous	-0.009	Destabilizing	0.081	N	0.572	neutral	None	None	None	None	I
L/E	0.2805	likely_benign	0.2764	benign	-0.111	Destabilizing	0.081	N	0.582	neutral	None	None	None	None	I
L/F	0.1055	likely_benign	0.1053	benign	-0.526	Destabilizing	None	N	0.299	neutral	N	0.475550036	None	None	I
L/G	0.3565	ambiguous	0.3796	ambiguous	-0.456	Destabilizing	0.035	N	0.549	neutral	None	None	None	None	I
L/H	0.1467	likely_benign	0.149	benign	0.106	Stabilizing	0.555	D	0.564	neutral	None	None	None	None	I
L/I	0.0804	likely_benign	0.0811	benign	-0.186	Destabilizing	0.081	N	0.447	neutral	None	None	None	None	I
L/K	0.1803	likely_benign	0.1787	benign	-0.158	Destabilizing	0.081	N	0.573	neutral	None	None	None	None	I
L/M	0.0901	likely_benign	0.0888	benign	-0.363	Destabilizing	0.484	N	0.518	neutral	N	0.475376678	None	None	I
L/N	0.1906	likely_benign	0.208	benign	0.023	Stabilizing	0.002	N	0.451	neutral	None	None	None	None	I
L/P	0.5655	likely_pathogenic	0.563	ambiguous	-0.208	Destabilizing	0.38	N	0.565	neutral	None	None	None	None	I
L/Q	0.1125	likely_benign	0.1159	benign	-0.178	Destabilizing	0.38	N	0.542	neutral	None	None	None	None	I
L/R	0.1503	likely_benign	0.1487	benign	0.296	Stabilizing	0.38	N	0.541	neutral	None	None	None	None	I
L/S	0.1407	likely_benign	0.1544	benign	-0.387	Destabilizing	None	N	0.327	neutral	N	0.358530864	None	None	I
L/T	0.1188	likely_benign	0.1254	benign	-0.384	Destabilizing	0.081	N	0.524	neutral	None	None	None	None	I
L/V	0.0745	likely_benign	0.0756	benign	-0.208	Destabilizing	0.027	N	0.476	neutral	N	0.41657909	None	None	I
L/W	0.2415	likely_benign	0.2425	benign	-0.558	Destabilizing	0.78	D	0.555	neutral	N	0.512894916	None	None	I
L/Y	0.2463	likely_benign	0.2508	benign	-0.289	Destabilizing	0.235	N	0.575	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.