TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35634	107125;107126;107127	chr2:178528851;178528850;178528849	chr2:179393578;179393577;179393576
N2AB	33993	102202;102203;102204	chr2:178528851;178528850;178528849	chr2:179393578;179393577;179393576
N2A	33066	99421;99422;99423	chr2:178528851;178528850;178528849	chr2:179393578;179393577;179393576
N2B	26569	79930;79931;79932	chr2:178528851;178528850;178528849	chr2:179393578;179393577;179393576
Novex-1	26694	80305;80306;80307	chr2:178528851;178528850;178528849	chr2:179393578;179393577;179393576
Novex-2	26761	80506;80507;80508	chr2:178528851;178528850;178528849	chr2:179393578;179393577;179393576
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Ig-167
• Domain position: 28
• Structural Position: 44
• Q(SASA): 0.2453
• 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
T/A	None	None	0.041	N	0.351	0.136	0.143124449307	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
T/A	0.1117	likely_benign	0.1158	benign	-0.621	Destabilizing	0.041	N	0.351	neutral	N	0.459772507	None	None	N
T/C	0.6938	likely_pathogenic	0.6838	pathogenic	-0.273	Destabilizing	0.944	D	0.557	neutral	None	None	None	None	N
T/D	0.4562	ambiguous	0.4756	ambiguous	-0.047	Destabilizing	0.388	N	0.486	neutral	None	None	None	None	N
T/E	0.3159	likely_benign	0.3181	benign	-0.13	Destabilizing	0.241	N	0.464	neutral	None	None	None	None	N
T/F	0.4464	ambiguous	0.4475	ambiguous	-1.111	Destabilizing	0.818	D	0.59	neutral	None	None	None	None	N
T/G	0.3171	likely_benign	0.327	benign	-0.747	Destabilizing	0.116	N	0.421	neutral	None	None	None	None	N
T/H	0.4098	ambiguous	0.4158	ambiguous	-1.096	Destabilizing	0.818	D	0.569	neutral	None	None	None	None	N
T/I	0.2852	likely_benign	0.288	benign	-0.399	Destabilizing	0.627	D	0.578	neutral	N	0.46046594	None	None	N
T/K	0.1952	likely_benign	0.2101	benign	-0.466	Destabilizing	0.241	N	0.477	neutral	None	None	None	None	N
T/L	0.179	likely_benign	0.1822	benign	-0.399	Destabilizing	0.388	N	0.459	neutral	None	None	None	None	N
T/M	0.1534	likely_benign	0.1511	benign	0.03	Stabilizing	0.932	D	0.57	neutral	None	None	None	None	N
T/N	0.1775	likely_benign	0.1859	benign	-0.204	Destabilizing	0.193	N	0.448	neutral	N	0.459772507	None	None	N
T/P	0.2878	likely_benign	0.3633	ambiguous	-0.446	Destabilizing	0.492	N	0.567	neutral	N	0.449544365	None	None	N
T/Q	0.2778	likely_benign	0.2812	benign	-0.529	Destabilizing	0.69	D	0.601	neutral	None	None	None	None	N
T/R	0.1633	likely_benign	0.1758	benign	-0.134	Destabilizing	0.69	D	0.587	neutral	None	None	None	None	N
T/S	0.142	likely_benign	0.1425	benign	-0.441	Destabilizing	None	N	0.115	neutral	N	0.415885657	None	None	N
T/V	0.2143	likely_benign	0.2084	benign	-0.446	Destabilizing	0.388	N	0.441	neutral	None	None	None	None	N
T/W	0.7691	likely_pathogenic	0.7666	pathogenic	-1.041	Destabilizing	0.981	D	0.562	neutral	None	None	None	None	N
T/Y	0.5039	ambiguous	0.5141	ambiguous	-0.791	Destabilizing	0.818	D	0.583	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.