TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	30539	91840;91841;91842	chr2:178550223;178550222;178550221	chr2:179414950;179414949;179414948
N2AB	28898	86917;86918;86919	chr2:178550223;178550222;178550221	chr2:179414950;179414949;179414948
N2A	27971	84136;84137;84138	chr2:178550223;178550222;178550221	chr2:179414950;179414949;179414948
N2B	21474	64645;64646;64647	chr2:178550223;178550222;178550221	chr2:179414950;179414949;179414948
Novex-1	21599	65020;65021;65022	chr2:178550223;178550222;178550221	chr2:179414950;179414949;179414948
Novex-2	21666	65221;65222;65223	chr2:178550223;178550222;178550221	chr2:179414950;179414949;179414948
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: Ig-149
• Domain position: 8
• Structural Position: 18
• Q(SASA): 0.7065
• Predicted PPI site: I

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	rs1553536395	-0.023	0.217	N	0.382	0.136	0.265010934533	gnomAD-2.1.1	4.03E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	8.9E-06	0
K/R	rs1553536395	-0.023	0.217	N	0.382	0.136	0.265010934533	gnomAD-4.0.0	5.47454E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	7.19661E-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	0.459	ambiguous	0.6023	pathogenic	-0.104	Destabilizing	0.996	D	0.651	neutral	None	None	None	None	I
K/C	0.7263	likely_pathogenic	0.7992	pathogenic	-0.345	Destabilizing	1.0	D	0.756	deleterious	None	None	None	None	I
K/D	0.7416	likely_pathogenic	0.8478	pathogenic	0.108	Stabilizing	0.999	D	0.651	neutral	None	None	None	None	I
K/E	0.3528	ambiguous	0.4903	ambiguous	0.143	Stabilizing	0.989	D	0.635	neutral	N	0.429663031	None	None	I
K/F	0.8157	likely_pathogenic	0.8987	pathogenic	-0.132	Destabilizing	1.0	D	0.709	prob.delet.	None	None	None	None	I
K/G	0.5912	likely_pathogenic	0.7267	pathogenic	-0.356	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	I
K/H	0.3013	likely_benign	0.3673	ambiguous	-0.609	Destabilizing	1.0	D	0.641	neutral	None	None	None	None	I
K/I	0.5165	ambiguous	0.6494	pathogenic	0.495	Stabilizing	1.0	D	0.722	prob.delet.	None	None	None	None	I
K/L	0.4515	ambiguous	0.5702	pathogenic	0.495	Stabilizing	0.999	D	0.618	neutral	None	None	None	None	I
K/M	0.3637	ambiguous	0.481	ambiguous	0.237	Stabilizing	1.0	D	0.645	neutral	D	0.526941648	None	None	I
K/N	0.5489	ambiguous	0.6862	pathogenic	0.01	Stabilizing	0.998	D	0.647	neutral	N	0.507219737	None	None	I
K/P	0.5855	likely_pathogenic	0.7286	pathogenic	0.325	Stabilizing	1.0	D	0.636	neutral	None	None	None	None	I
K/Q	0.165	likely_benign	0.2039	benign	-0.134	Destabilizing	0.997	D	0.651	neutral	N	0.500427051	None	None	I
K/R	0.0809	likely_benign	0.0837	benign	-0.209	Destabilizing	0.217	N	0.382	neutral	N	0.45336661	None	None	I
K/S	0.5384	ambiguous	0.6731	pathogenic	-0.535	Destabilizing	0.996	D	0.65	neutral	None	None	None	None	I
K/T	0.2609	likely_benign	0.3619	ambiguous	-0.333	Destabilizing	0.998	D	0.629	neutral	N	0.49277036	None	None	I
K/V	0.4596	ambiguous	0.5858	pathogenic	0.325	Stabilizing	0.999	D	0.689	prob.neutral	None	None	None	None	I
K/W	0.7911	likely_pathogenic	0.8709	pathogenic	-0.094	Destabilizing	1.0	D	0.755	deleterious	None	None	None	None	I
K/Y	0.6921	likely_pathogenic	0.8031	pathogenic	0.23	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I

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.