TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	31669	95230;95231;95232	chr2:178546326;178546325;178546324	chr2:179411053;179411052;179411051
N2AB	30028	90307;90308;90309	chr2:178546326;178546325;178546324	chr2:179411053;179411052;179411051
N2A	29101	87526;87527;87528	chr2:178546326;178546325;178546324	chr2:179411053;179411052;179411051
N2B	22604	68035;68036;68037	chr2:178546326;178546325;178546324	chr2:179411053;179411052;179411051
Novex-1	22729	68410;68411;68412	chr2:178546326;178546325;178546324	chr2:179411053;179411052;179411051
Novex-2	22796	68611;68612;68613	chr2:178546326;178546325;178546324	chr2:179411053;179411052;179411051
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-152
• Domain position: 49
• Structural Position: 134
• Q(SASA): 0.6461
• 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
K/Q	None	None	0.988	N	0.525	0.334	0.304760801415	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	6.07533E-05	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
K/A	0.4559	ambiguous	0.4124	ambiguous	0.024	Stabilizing	0.759	D	0.455	neutral	None	None	None	None	N
K/C	0.7136	likely_pathogenic	0.6641	pathogenic	-0.351	Destabilizing	0.999	D	0.531	neutral	None	None	None	None	N
K/D	0.5845	likely_pathogenic	0.5333	ambiguous	-0.034	Destabilizing	0.939	D	0.496	neutral	None	None	None	None	N
K/E	0.2728	likely_benign	0.2344	benign	-0.041	Destabilizing	0.92	D	0.453	neutral	N	0.469373425	None	None	N
K/F	0.8357	likely_pathogenic	0.7955	pathogenic	-0.278	Destabilizing	0.997	D	0.533	neutral	None	None	None	None	N
K/G	0.4396	ambiguous	0.3973	ambiguous	-0.13	Destabilizing	0.939	D	0.503	neutral	None	None	None	None	N
K/H	0.3567	ambiguous	0.3202	benign	-0.298	Destabilizing	0.999	D	0.501	neutral	None	None	None	None	N
K/I	0.5362	ambiguous	0.4976	ambiguous	0.344	Stabilizing	0.976	D	0.533	neutral	N	0.501083199	None	None	N
K/L	0.4381	ambiguous	0.4029	ambiguous	0.344	Stabilizing	0.939	D	0.525	neutral	None	None	None	None	N
K/M	0.3211	likely_benign	0.2925	benign	0.076	Stabilizing	0.997	D	0.501	neutral	None	None	None	None	N
K/N	0.3984	ambiguous	0.3576	ambiguous	0.103	Stabilizing	0.92	D	0.455	neutral	N	0.440725386	None	None	N
K/P	0.7123	likely_pathogenic	0.6773	pathogenic	0.263	Stabilizing	0.997	D	0.494	neutral	None	None	None	None	N
K/Q	0.149	likely_benign	0.1347	benign	-0.051	Destabilizing	0.988	D	0.525	neutral	N	0.481110571	None	None	N
K/R	0.0867	likely_benign	0.0828	benign	-0.049	Destabilizing	0.959	D	0.466	neutral	N	0.491058206	None	None	N
K/S	0.405	ambiguous	0.3574	ambiguous	-0.335	Destabilizing	0.373	N	0.224	neutral	None	None	None	None	N
K/T	0.2181	likely_benign	0.1929	benign	-0.209	Destabilizing	0.061	N	0.24	neutral	N	0.388432484	None	None	N
K/V	0.4792	ambiguous	0.4385	ambiguous	0.263	Stabilizing	0.939	D	0.52	neutral	None	None	None	None	N
K/W	0.8118	likely_pathogenic	0.7648	pathogenic	-0.34	Destabilizing	0.999	D	0.587	neutral	None	None	None	None	N
K/Y	0.6943	likely_pathogenic	0.6305	pathogenic	0.022	Stabilizing	0.997	D	0.541	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.