TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21599	65020;65021;65022	chr2:178584846;178584845;178584844	chr2:179449573;179449572;179449571
N2AB	19958	60097;60098;60099	chr2:178584846;178584845;178584844	chr2:179449573;179449572;179449571
N2A	19031	57316;57317;57318	chr2:178584846;178584845;178584844	chr2:179449573;179449572;179449571
N2B	12534	37825;37826;37827	chr2:178584846;178584845;178584844	chr2:179449573;179449572;179449571
Novex-1	12659	38200;38201;38202	chr2:178584846;178584845;178584844	chr2:179449573;179449572;179449571
Novex-2	12726	38401;38402;38403	chr2:178584846;178584845;178584844	chr2:179449573;179449572;179449571
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Fn3-44
• Domain position: 41
• Structural Position: 42
• Q(SASA): 0.1852
• 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	0.64	N	0.399	0.221	0.202949470691	gnomAD-4.0.0	1.59204E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.85984E-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	0.9558	likely_pathogenic	0.9579	pathogenic	-1.42	Destabilizing	0.998	D	0.689	prob.neutral	None	None	None	None	N
K/C	0.9168	likely_pathogenic	0.9113	pathogenic	-1.358	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/D	0.9961	likely_pathogenic	0.9965	pathogenic	-1.733	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
K/E	0.9323	likely_pathogenic	0.9372	pathogenic	-1.41	Destabilizing	0.996	D	0.685	prob.neutral	N	0.513844718	None	None	N
K/F	0.9698	likely_pathogenic	0.9669	pathogenic	-0.699	Destabilizing	1.0	D	0.844	deleterious	None	None	None	None	N
K/G	0.9816	likely_pathogenic	0.9829	pathogenic	-1.926	Destabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
K/H	0.7914	likely_pathogenic	0.7995	pathogenic	-1.681	Destabilizing	1.0	D	0.825	deleterious	None	None	None	None	N
K/I	0.7907	likely_pathogenic	0.7887	pathogenic	0.024	Stabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
K/L	0.8074	likely_pathogenic	0.8129	pathogenic	0.024	Stabilizing	1.0	D	0.77	deleterious	None	None	None	None	N
K/M	0.5923	likely_pathogenic	0.6057	pathogenic	-0.286	Destabilizing	1.0	D	0.818	deleterious	N	0.52128982	None	None	N
K/N	0.9754	likely_pathogenic	0.9781	pathogenic	-1.74	Destabilizing	0.999	D	0.811	deleterious	D	0.531948973	None	None	N
K/P	0.9993	likely_pathogenic	0.9993	pathogenic	-0.438	Destabilizing	1.0	D	0.832	deleterious	None	None	None	None	N
K/Q	0.6096	likely_pathogenic	0.6316	pathogenic	-1.352	Destabilizing	0.999	D	0.812	deleterious	N	0.466279903	None	None	N
K/R	0.168	likely_benign	0.1761	benign	-0.755	Destabilizing	0.64	D	0.399	neutral	N	0.51268898	None	None	N
K/S	0.9749	likely_pathogenic	0.9782	pathogenic	-2.329	Highly Destabilizing	0.998	D	0.719	prob.delet.	None	None	None	None	N
K/T	0.8317	likely_pathogenic	0.8495	pathogenic	-1.725	Destabilizing	0.999	D	0.784	deleterious	N	0.48509172	None	None	N
K/V	0.7714	likely_pathogenic	0.7605	pathogenic	-0.438	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
K/W	0.9673	likely_pathogenic	0.9672	pathogenic	-0.697	Destabilizing	1.0	D	0.797	deleterious	None	None	None	None	N
K/Y	0.885	likely_pathogenic	0.8844	pathogenic	-0.359	Destabilizing	1.0	D	0.854	deleterious	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.