TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	18714	56365;56366;56367	chr2:178599761;178599760;178599759	chr2:179464488;179464487;179464486
N2AB	17073	51442;51443;51444	chr2:178599761;178599760;178599759	chr2:179464488;179464487;179464486
N2A	16146	48661;48662;48663	chr2:178599761;178599760;178599759	chr2:179464488;179464487;179464486
N2B	9649	29170;29171;29172	chr2:178599761;178599760;178599759	chr2:179464488;179464487;179464486
Novex-1	9774	29545;29546;29547	chr2:178599761;178599760;178599759	chr2:179464488;179464487;179464486
Novex-2	9841	29746;29747;29748	chr2:178599761;178599760;178599759	chr2:179464488;179464487;179464486
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCG
• RefSeq wild type template codon: GGC
• Domain: Ig-116
• Domain position: 27
• Structural Position: 44
• Q(SASA): 0.1935
• 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
P/L	rs2052778665	None	1.0	D	0.761	0.82	0.889922392587	gnomAD-3.1.2	1.32E-05	None	None	None	None	I	None	2.42E-05	0	0	0	0	None	9.43E-05	0	0	0	0
P/L	rs2052778665	None	1.0	D	0.761	0.82	0.889922392587	gnomAD-4.0.0	3.10147E-06	None	None	None	None	I	None	4.01059E-05	0	None	0	0	None	3.1294E-05	0	0	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
P/A	0.8442	likely_pathogenic	0.8143	pathogenic	-1.354	Destabilizing	1.0	D	0.757	deleterious	N	0.511520764	None	None	I
P/C	0.9838	likely_pathogenic	0.9817	pathogenic	-1.001	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	I
P/D	0.9993	likely_pathogenic	0.9992	pathogenic	-0.744	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
P/E	0.9981	likely_pathogenic	0.9978	pathogenic	-0.71	Destabilizing	1.0	D	0.781	deleterious	None	None	None	None	I
P/F	0.9993	likely_pathogenic	0.9991	pathogenic	-0.989	Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	I
P/G	0.9898	likely_pathogenic	0.9886	pathogenic	-1.702	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/H	0.9967	likely_pathogenic	0.9963	pathogenic	-1.246	Destabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	I
P/I	0.9932	likely_pathogenic	0.9897	pathogenic	-0.494	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	I
P/K	0.999	likely_pathogenic	0.9987	pathogenic	-1.002	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	I
P/L	0.9667	likely_pathogenic	0.9494	pathogenic	-0.494	Destabilizing	1.0	D	0.761	deleterious	D	0.562120091	None	None	I
P/M	0.9961	likely_pathogenic	0.9945	pathogenic	-0.481	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	I
P/N	0.9989	likely_pathogenic	0.9987	pathogenic	-0.861	Destabilizing	1.0	D	0.765	deleterious	None	None	None	None	I
P/Q	0.9951	likely_pathogenic	0.9941	pathogenic	-0.938	Destabilizing	1.0	D	0.779	deleterious	D	0.566682902	None	None	I
P/R	0.995	likely_pathogenic	0.994	pathogenic	-0.634	Destabilizing	1.0	D	0.765	deleterious	D	0.566682902	None	None	I
P/S	0.9784	likely_pathogenic	0.9747	pathogenic	-1.48	Destabilizing	1.0	D	0.784	deleterious	D	0.554819618	None	None	I
P/T	0.982	likely_pathogenic	0.9751	pathogenic	-1.317	Destabilizing	1.0	D	0.783	deleterious	D	0.566175923	None	None	I
P/V	0.9763	likely_pathogenic	0.9683	pathogenic	-0.745	Destabilizing	1.0	D	0.751	deleterious	None	None	None	None	I
P/W	0.9997	likely_pathogenic	0.9997	pathogenic	-1.19	Destabilizing	1.0	D	0.688	prob.neutral	None	None	None	None	I
P/Y	0.9995	likely_pathogenic	0.9994	pathogenic	-0.858	Destabilizing	1.0	D	0.747	deleterious	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.