TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	5943	18052;18053;18054	chr2:178730706;178730705;178730704	chr2:179595433;179595432;179595431
N2AB	5626	17101;17102;17103	chr2:178730706;178730705;178730704	chr2:179595433;179595432;179595431
N2A	4699	14320;14321;14322	chr2:178730706;178730705;178730704	chr2:179595433;179595432;179595431
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-43
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.3704
• 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
A/S	rs1421739163	None	0.079	N	0.214	0.069	0.183819452728	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
A/S	rs1421739163	None	0.079	N	0.214	0.069	0.183819452728	gnomAD-4.0.0	2.03E-06	None	None	None	None	N	None	1.74764E-05	0	None	0	0	None	0	0	1.20493E-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
A/C	0.6999	likely_pathogenic	0.6605	pathogenic	-0.904	Destabilizing	0.999	D	0.522	neutral	None	None	None	None	N
A/D	0.6462	likely_pathogenic	0.6094	pathogenic	-0.478	Destabilizing	0.982	D	0.532	neutral	N	0.476531471	None	None	N
A/E	0.5422	ambiguous	0.5223	ambiguous	-0.559	Destabilizing	0.953	D	0.497	neutral	None	None	None	None	N
A/F	0.489	ambiguous	0.4492	ambiguous	-0.858	Destabilizing	0.993	D	0.631	neutral	None	None	None	None	N
A/G	0.2108	likely_benign	0.227	benign	-0.764	Destabilizing	0.76	D	0.441	neutral	N	0.492578359	None	None	N
A/H	0.6565	likely_pathogenic	0.6103	pathogenic	-0.812	Destabilizing	0.999	D	0.62	neutral	None	None	None	None	N
A/I	0.5613	ambiguous	0.5018	ambiguous	-0.254	Destabilizing	0.993	D	0.555	neutral	None	None	None	None	N
A/K	0.7395	likely_pathogenic	0.7235	pathogenic	-0.926	Destabilizing	0.953	D	0.486	neutral	None	None	None	None	N
A/L	0.3526	ambiguous	0.2991	benign	-0.254	Destabilizing	0.953	D	0.489	neutral	None	None	None	None	N
A/M	0.4002	ambiguous	0.3462	ambiguous	-0.322	Destabilizing	0.999	D	0.552	neutral	None	None	None	None	N
A/N	0.4835	ambiguous	0.4204	ambiguous	-0.623	Destabilizing	0.986	D	0.529	neutral	None	None	None	None	N
A/P	0.9689	likely_pathogenic	0.9691	pathogenic	-0.322	Destabilizing	0.991	D	0.555	neutral	N	0.48854362	None	None	N
A/Q	0.5373	ambiguous	0.5021	ambiguous	-0.798	Destabilizing	0.993	D	0.571	neutral	None	None	None	None	N
A/R	0.6354	likely_pathogenic	0.6176	pathogenic	-0.554	Destabilizing	0.986	D	0.563	neutral	None	None	None	None	N
A/S	0.098	likely_benign	0.0957	benign	-0.976	Destabilizing	0.079	N	0.214	neutral	N	0.378906136	None	None	N
A/T	0.1344	likely_benign	0.1211	benign	-0.951	Destabilizing	0.885	D	0.402	neutral	N	0.459252432	None	None	N
A/V	0.2987	likely_benign	0.2605	benign	-0.322	Destabilizing	0.939	D	0.453	neutral	N	0.473376522	None	None	N
A/W	0.8557	likely_pathogenic	0.8257	pathogenic	-1.092	Destabilizing	0.999	D	0.65	neutral	None	None	None	None	N
A/Y	0.6195	likely_pathogenic	0.5746	pathogenic	-0.706	Destabilizing	0.998	D	0.627	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.