TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5064	15415;15416;15417	chr2:178734734;178734733;178734732	chr2:179599461;179599460;179599459
N2AB	4747	14464;14465;14466	chr2:178734734;178734733;178734732	chr2:179599461;179599460;179599459
N2A	3820	11683;11684;11685	chr2:178734734;178734733;178734732	chr2:179599461;179599460;179599459
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: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-33
• Domain position: 84
• Structural Position: 168
• Q(SASA): 0.2976
• 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/N	None	None	0.001	N	0.38	0.129	0.17258766438	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.9375E-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
S/A	0.1125	likely_benign	0.1022	benign	-0.691	Destabilizing	0.072	N	0.548	neutral	None	None	None	None	N
S/C	0.1781	likely_benign	0.1912	benign	-0.407	Destabilizing	0.883	D	0.639	neutral	D	0.617695089	None	None	N
S/D	0.5688	likely_pathogenic	0.4999	ambiguous	0.031	Stabilizing	0.157	N	0.455	neutral	None	None	None	None	N
S/E	0.7095	likely_pathogenic	0.6182	pathogenic	-0.028	Destabilizing	0.272	N	0.449	neutral	None	None	None	None	N
S/F	0.2031	likely_benign	0.1952	benign	-1.111	Destabilizing	0.726	D	0.711	prob.delet.	None	None	None	None	N
S/G	0.1353	likely_benign	0.1298	benign	-0.864	Destabilizing	0.22	N	0.51	neutral	D	0.64023221	None	None	N
S/H	0.3349	likely_benign	0.3212	benign	-1.314	Destabilizing	0.909	D	0.646	neutral	None	None	None	None	N
S/I	0.1805	likely_benign	0.1716	benign	-0.353	Destabilizing	0.331	N	0.684	prob.neutral	D	0.554732472	None	None	N
S/K	0.7378	likely_pathogenic	0.6416	pathogenic	-0.633	Destabilizing	0.272	N	0.458	neutral	None	None	None	None	N
S/L	0.1308	likely_benign	0.1296	benign	-0.353	Destabilizing	0.157	N	0.576	neutral	None	None	None	None	N
S/M	0.2296	likely_benign	0.2292	benign	-0.035	Destabilizing	0.909	D	0.633	neutral	None	None	None	None	N
S/N	0.149	likely_benign	0.1447	benign	-0.392	Destabilizing	0.001	N	0.38	neutral	N	0.509599753	None	None	N
S/P	0.9235	likely_pathogenic	0.9234	pathogenic	-0.435	Destabilizing	0.726	D	0.647	neutral	None	None	None	None	N
S/Q	0.5794	likely_pathogenic	0.5127	ambiguous	-0.62	Destabilizing	0.726	D	0.507	neutral	None	None	None	None	N
S/R	0.6011	likely_pathogenic	0.5076	ambiguous	-0.417	Destabilizing	0.497	N	0.643	neutral	N	0.510306457	None	None	N
S/T	0.0741	likely_benign	0.0753	benign	-0.499	Destabilizing	0.001	N	0.363	neutral	N	0.503103606	None	None	N
S/V	0.2089	likely_benign	0.1956	benign	-0.435	Destabilizing	0.396	N	0.61	neutral	None	None	None	None	N
S/W	0.476	ambiguous	0.4684	ambiguous	-1.057	Destabilizing	0.968	D	0.711	prob.delet.	None	None	None	None	N
S/Y	0.2282	likely_benign	0.22	benign	-0.811	Destabilizing	0.726	D	0.713	prob.delet.	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.