TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16100	48523;48524;48525	chr2:178616493;178616492;178616491	chr2:179481220;179481219;179481218
N2AB	14459	43600;43601;43602	chr2:178616493;178616492;178616491	chr2:179481220;179481219;179481218
N2A	13532	40819;40820;40821	chr2:178616493;178616492;178616491	chr2:179481220;179481219;179481218
N2B	7035	21328;21329;21330	chr2:178616493;178616492;178616491	chr2:179481220;179481219;179481218
Novex-1	7160	21703;21704;21705	chr2:178616493;178616492;178616491	chr2:179481220;179481219;179481218
Novex-2	7227	21904;21905;21906	chr2:178616493;178616492;178616491	chr2:179481220;179481219;179481218
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: Fn3-4
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.8765
• 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/E	None	None	0.999	N	0.631	0.369	0.28798054836	gnomAD-4.0.0	1.59465E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43451E-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	0.7375	likely_pathogenic	0.8092	pathogenic	-0.057	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	N
K/C	0.9044	likely_pathogenic	0.9286	pathogenic	-0.554	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	N
K/D	0.8499	likely_pathogenic	0.8935	pathogenic	-0.364	Destabilizing	1.0	D	0.632	neutral	None	None	None	None	N
K/E	0.5765	likely_pathogenic	0.6683	pathogenic	-0.386	Destabilizing	0.999	D	0.631	neutral	N	0.474528896	None	None	N
K/F	0.9466	likely_pathogenic	0.962	pathogenic	-0.431	Destabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	N
K/G	0.7286	likely_pathogenic	0.7742	pathogenic	-0.161	Destabilizing	1.0	D	0.605	neutral	None	None	None	None	N
K/H	0.5819	likely_pathogenic	0.6323	pathogenic	-0.229	Destabilizing	1.0	D	0.662	neutral	None	None	None	None	N
K/I	0.7961	likely_pathogenic	0.8506	pathogenic	0.134	Stabilizing	1.0	D	0.715	prob.delet.	D	0.532858515	None	None	N
K/L	0.6917	likely_pathogenic	0.759	pathogenic	0.134	Stabilizing	1.0	D	0.605	neutral	None	None	None	None	N
K/M	0.5675	likely_pathogenic	0.6518	pathogenic	-0.172	Destabilizing	1.0	D	0.659	neutral	None	None	None	None	N
K/N	0.7345	likely_pathogenic	0.7937	pathogenic	-0.108	Destabilizing	1.0	D	0.654	neutral	N	0.476635385	None	None	N
K/P	0.7928	likely_pathogenic	0.8474	pathogenic	0.092	Stabilizing	1.0	D	0.622	neutral	None	None	None	None	N
K/Q	0.3086	likely_benign	0.3642	ambiguous	-0.257	Destabilizing	1.0	D	0.643	neutral	N	0.464399576	None	None	N
K/R	0.1134	likely_benign	0.1174	benign	-0.192	Destabilizing	0.999	D	0.581	neutral	N	0.468511957	None	None	N
K/S	0.7801	likely_pathogenic	0.8389	pathogenic	-0.467	Destabilizing	0.999	D	0.608	neutral	None	None	None	None	N
K/T	0.5421	ambiguous	0.6234	pathogenic	-0.382	Destabilizing	1.0	D	0.617	neutral	N	0.478756224	None	None	N
K/V	0.7333	likely_pathogenic	0.7955	pathogenic	0.092	Stabilizing	1.0	D	0.654	neutral	None	None	None	None	N
K/W	0.9261	likely_pathogenic	0.9435	pathogenic	-0.533	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
K/Y	0.8668	likely_pathogenic	0.8914	pathogenic	-0.19	Destabilizing	1.0	D	0.678	prob.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.