TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	27131	81616;81617;81618	chr2:178564741;178564740;178564739	chr2:179429468;179429467;179429466
N2AB	25490	76693;76694;76695	chr2:178564741;178564740;178564739	chr2:179429468;179429467;179429466
N2A	24563	73912;73913;73914	chr2:178564741;178564740;178564739	chr2:179429468;179429467;179429466
N2B	18066	54421;54422;54423	chr2:178564741;178564740;178564739	chr2:179429468;179429467;179429466
Novex-1	18191	54796;54797;54798	chr2:178564741;178564740;178564739	chr2:179429468;179429467;179429466
Novex-2	18258	54997;54998;54999	chr2:178564741;178564740;178564739	chr2:179429468;179429467;179429466
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: Fn3-85
• Domain position: 60
• Structural Position: 90
• Q(SASA): 0.4047
• 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/R	None	None	0.005	N	0.198	0.083	0.158396225186	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.3125E-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
K/A	0.1958	likely_benign	0.2113	benign	-0.628	Destabilizing	0.525	D	0.423	neutral	None	None	None	None	N
K/C	0.3391	likely_benign	0.335	benign	-0.752	Destabilizing	0.998	D	0.578	neutral	None	None	None	None	N
K/D	0.5019	ambiguous	0.527	ambiguous	-0.361	Destabilizing	0.842	D	0.482	neutral	None	None	None	None	N
K/E	0.1399	likely_benign	0.157	benign	-0.193	Destabilizing	0.625	D	0.38	neutral	N	0.399422189	None	None	N
K/F	0.4988	ambiguous	0.53	ambiguous	-0.1	Destabilizing	0.974	D	0.581	neutral	None	None	None	None	N
K/G	0.3595	ambiguous	0.3813	ambiguous	-1.033	Destabilizing	0.842	D	0.503	neutral	None	None	None	None	N
K/H	0.1637	likely_benign	0.1644	benign	-1.15	Destabilizing	0.037	N	0.361	neutral	None	None	None	None	N
K/I	0.177	likely_benign	0.1899	benign	0.445	Stabilizing	0.934	D	0.584	neutral	N	0.46499382	None	None	N
K/L	0.2196	likely_benign	0.2369	benign	0.445	Stabilizing	0.728	D	0.503	neutral	None	None	None	None	N
K/M	0.1404	likely_benign	0.1483	benign	0.076	Stabilizing	0.991	D	0.555	neutral	None	None	None	None	N
K/N	0.2946	likely_benign	0.3035	benign	-0.856	Destabilizing	0.801	D	0.358	neutral	N	0.443386397	None	None	N
K/P	0.9104	likely_pathogenic	0.9244	pathogenic	0.116	Stabilizing	0.974	D	0.575	neutral	None	None	None	None	N
K/Q	0.0883	likely_benign	0.0918	benign	-0.757	Destabilizing	0.801	D	0.415	neutral	N	0.406137518	None	None	N
K/R	0.0655	likely_benign	0.0661	benign	-0.676	Destabilizing	0.005	N	0.198	neutral	N	0.381836506	None	None	N
K/S	0.2259	likely_benign	0.2355	benign	-1.434	Destabilizing	0.728	D	0.375	neutral	None	None	None	None	N
K/T	0.0864	likely_benign	0.0947	benign	-1.047	Destabilizing	0.051	N	0.439	neutral	N	0.399824834	None	None	N
K/V	0.1484	likely_benign	0.1621	benign	0.116	Stabilizing	0.728	D	0.544	neutral	None	None	None	None	N
K/W	0.5744	likely_pathogenic	0.5783	pathogenic	-0.055	Destabilizing	0.998	D	0.594	neutral	None	None	None	None	N
K/Y	0.3545	ambiguous	0.3674	ambiguous	0.233	Stabilizing	0.949	D	0.588	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.