TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9229	27910;27911;27912	chr2:178712145;178712144;178712143	chr2:179576872;179576871;179576870
N2AB	8912	26959;26960;26961	chr2:178712145;178712144;178712143	chr2:179576872;179576871;179576870
N2A	7985	24178;24179;24180	chr2:178712145;178712144;178712143	chr2:179576872;179576871;179576870
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-78
• Domain position: 25
• Structural Position: 38
• Q(SASA): 0.186
• 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	None	None	0.124	N	0.537	0.123	0.253205268125	gnomAD-4.0.0	7.20193E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	7.87501E-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	0.6641	likely_pathogenic	0.694	pathogenic	-0.622	Destabilizing	0.968	D	0.627	neutral	None	None	None	None	N
A/D	0.246	likely_benign	0.273	benign	-1.146	Destabilizing	0.124	N	0.599	neutral	N	0.431009825	None	None	N
A/E	0.2663	likely_benign	0.2569	benign	-1.11	Destabilizing	0.011	N	0.379	neutral	None	None	None	None	N
A/F	0.4292	ambiguous	0.4815	ambiguous	-0.721	Destabilizing	0.89	D	0.639	neutral	None	None	None	None	N
A/G	0.1349	likely_benign	0.1642	benign	-1.068	Destabilizing	None	N	0.25	neutral	N	0.450558378	None	None	N
A/H	0.5432	ambiguous	0.5631	ambiguous	-1.171	Destabilizing	0.909	D	0.632	neutral	None	None	None	None	N
A/I	0.4407	ambiguous	0.468	ambiguous	-0.054	Destabilizing	0.726	D	0.665	neutral	None	None	None	None	N
A/K	0.5089	ambiguous	0.5081	ambiguous	-1.094	Destabilizing	0.157	N	0.611	neutral	None	None	None	None	N
A/L	0.2622	likely_benign	0.2681	benign	-0.054	Destabilizing	0.272	N	0.596	neutral	None	None	None	None	N
A/M	0.3473	ambiguous	0.355	ambiguous	-0.082	Destabilizing	0.968	D	0.625	neutral	None	None	None	None	N
A/N	0.3306	likely_benign	0.3424	ambiguous	-0.942	Destabilizing	0.567	D	0.599	neutral	None	None	None	None	N
A/P	0.8962	likely_pathogenic	0.9464	pathogenic	-0.248	Destabilizing	0.667	D	0.64	neutral	N	0.494797817	None	None	N
A/Q	0.347	ambiguous	0.3271	benign	-0.996	Destabilizing	0.011	N	0.461	neutral	None	None	None	None	N
A/R	0.4251	ambiguous	0.4237	ambiguous	-0.825	Destabilizing	0.396	N	0.627	neutral	None	None	None	None	N
A/S	0.105	likely_benign	0.103	benign	-1.297	Destabilizing	0.124	N	0.537	neutral	N	0.437895725	None	None	N
A/T	0.1458	likely_benign	0.1534	benign	-1.155	Destabilizing	0.22	N	0.58	neutral	N	0.441205389	None	None	N
A/V	0.2288	likely_benign	0.2468	benign	-0.248	Destabilizing	0.364	N	0.579	neutral	N	0.479033058	None	None	N
A/W	0.7817	likely_pathogenic	0.8268	pathogenic	-1.183	Destabilizing	0.968	D	0.682	prob.neutral	None	None	None	None	N
A/Y	0.562	ambiguous	0.6123	pathogenic	-0.699	Destabilizing	0.89	D	0.64	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.