TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5962	18109;18110;18111	chr2:178730649;178730648;178730647	chr2:179595376;179595375;179595374
N2AB	5645	17158;17159;17160	chr2:178730649;178730648;178730647	chr2:179595376;179595375;179595374
N2A	4718	14377;14378;14379	chr2:178730649;178730648;178730647	chr2:179595376;179595375;179595374
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: AGT
• RefSeq wild type template codon: TCA
• Domain: Ig-43
• Domain position: 44
• Structural Position: 73
• Q(SASA): 0.2317
• 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/G	None	None	0.001	N	0.135	0.06	0.110078149338	gnomAD-4.0.0	2.05278E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.6986E-06	0	0
S/I	None	None	0.963	N	0.375	0.399	0.405839309607	gnomAD-4.0.0	2.40064E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.21507E-04	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	0.1662	likely_benign	0.1588	benign	-0.469	Destabilizing	0.25	N	0.377	neutral	None	None	None	None	N
S/C	0.2634	likely_benign	0.2275	benign	-0.353	Destabilizing	0.99	D	0.304	neutral	N	0.475676609	None	None	N
S/D	0.4847	ambiguous	0.4547	ambiguous	0.604	Stabilizing	0.002	N	0.143	neutral	None	None	None	None	N
S/E	0.8027	likely_pathogenic	0.8003	pathogenic	0.545	Stabilizing	0.25	N	0.384	neutral	None	None	None	None	N
S/F	0.6085	likely_pathogenic	0.5938	pathogenic	-0.998	Destabilizing	0.972	D	0.361	neutral	None	None	None	None	N
S/G	0.087	likely_benign	0.0813	benign	-0.609	Destabilizing	0.001	N	0.135	neutral	N	0.412284338	None	None	N
S/H	0.6533	likely_pathogenic	0.6413	pathogenic	-0.958	Destabilizing	0.972	D	0.28	neutral	None	None	None	None	N
S/I	0.6101	likely_pathogenic	0.609	pathogenic	-0.227	Destabilizing	0.963	D	0.375	neutral	N	0.477562713	None	None	N
S/K	0.883	likely_pathogenic	0.881	pathogenic	-0.3	Destabilizing	0.617	D	0.362	neutral	None	None	None	None	N
S/L	0.2291	likely_benign	0.2165	benign	-0.227	Destabilizing	0.766	D	0.371	neutral	None	None	None	None	N
S/M	0.4103	ambiguous	0.3907	ambiguous	-0.196	Destabilizing	0.992	D	0.283	neutral	None	None	None	None	N
S/N	0.1978	likely_benign	0.1821	benign	-0.152	Destabilizing	0.549	D	0.425	neutral	N	0.485128658	None	None	N
S/P	0.843	likely_pathogenic	0.8151	pathogenic	-0.278	Destabilizing	0.972	D	0.308	neutral	None	None	None	None	N
S/Q	0.7948	likely_pathogenic	0.7915	pathogenic	-0.283	Destabilizing	0.92	D	0.365	neutral	None	None	None	None	N
S/R	0.8444	likely_pathogenic	0.8358	pathogenic	-0.171	Destabilizing	0.896	D	0.313	neutral	N	0.467661212	None	None	N
S/T	0.0893	likely_benign	0.0862	benign	-0.271	Destabilizing	0.712	D	0.421	neutral	N	0.509082954	None	None	N
S/V	0.5181	ambiguous	0.5055	ambiguous	-0.278	Destabilizing	0.92	D	0.394	neutral	None	None	None	None	N
S/W	0.7355	likely_pathogenic	0.7115	pathogenic	-1.013	Destabilizing	0.992	D	0.489	neutral	None	None	None	None	N
S/Y	0.5659	likely_pathogenic	0.5431	ambiguous	-0.712	Destabilizing	0.972	D	0.361	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.