TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	1313	4162;4163;4164	chr2:178779255;178779254;178779253	chr2:179643982;179643981;179643980
N2AB	1313	4162;4163;4164	chr2:178779255;178779254;178779253	chr2:179643982;179643981;179643980
N2A	1313	4162;4163;4164	chr2:178779255;178779254;178779253	chr2:179643982;179643981;179643980
N2B	1267	4024;4025;4026	chr2:178779255;178779254;178779253	chr2:179643982;179643981;179643980
Novex-1	1267	4024;4025;4026	chr2:178779255;178779254;178779253	chr2:179643982;179643981;179643980
Novex-2	1267	4024;4025;4026	chr2:178779255;178779254;178779253	chr2:179643982;179643981;179643980
Novex-3	1313	4162;4163;4164	chr2:178779255;178779254;178779253	chr2:179643982;179643981;179643980

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAG
• RefSeq wild type template codon: TTC
• Domain: Ig-5
• Domain position: 23
• Structural Position: 34
• Q(SASA): 0.375
• 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/E	None	None	0.996	N	0.484	0.48	0.411531665326	gnomAD-4.0.0	6.84211E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99418E-07	0	0
K/N	None	None	0.999	N	0.679	0.37	0.250579442822	gnomAD-4.0.0	6.84239E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	0	1.15945E-05	0
K/Q	None	None	0.999	N	0.669	0.482	0.289474373501	gnomAD-4.0.0	6.84211E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99418E-07	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	0.7468	likely_pathogenic	0.7812	pathogenic	-0.41	Destabilizing	0.998	D	0.579	neutral	None	None	None	None	I
K/C	0.8872	likely_pathogenic	0.9053	pathogenic	-0.613	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
K/D	0.9368	likely_pathogenic	0.9465	pathogenic	-0.682	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	I
K/E	0.5495	ambiguous	0.5787	pathogenic	-0.621	Destabilizing	0.996	D	0.484	neutral	N	0.502574004	None	None	I
K/F	0.9421	likely_pathogenic	0.952	pathogenic	-0.533	Destabilizing	1.0	D	0.75	deleterious	None	None	None	None	I
K/G	0.8765	likely_pathogenic	0.8905	pathogenic	-0.716	Destabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
K/H	0.4848	ambiguous	0.5319	ambiguous	-1.2	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
K/I	0.6412	likely_pathogenic	0.6693	pathogenic	0.356	Stabilizing	1.0	D	0.757	deleterious	None	None	None	None	I
K/L	0.6789	likely_pathogenic	0.7134	pathogenic	0.356	Stabilizing	1.0	D	0.707	prob.neutral	None	None	None	None	I
K/M	0.5416	ambiguous	0.5714	pathogenic	0.492	Stabilizing	1.0	D	0.751	deleterious	D	0.542184192	None	None	I
K/N	0.8197	likely_pathogenic	0.8428	pathogenic	-0.474	Destabilizing	0.999	D	0.679	prob.neutral	N	0.512471889	None	None	I
K/P	0.985	likely_pathogenic	0.9882	pathogenic	0.131	Stabilizing	1.0	D	0.76	deleterious	None	None	None	None	I
K/Q	0.2337	likely_benign	0.2582	benign	-0.728	Destabilizing	0.999	D	0.669	neutral	N	0.505863885	None	None	I
K/R	0.0935	likely_benign	0.0991	benign	-0.421	Destabilizing	0.64	D	0.341	neutral	N	0.458147416	None	None	I
K/S	0.797	likely_pathogenic	0.825	pathogenic	-1.027	Destabilizing	0.998	D	0.556	neutral	None	None	None	None	I
K/T	0.4623	ambiguous	0.4947	ambiguous	-0.785	Destabilizing	0.999	D	0.735	prob.delet.	N	0.506712461	None	None	I
K/V	0.6001	likely_pathogenic	0.6297	pathogenic	0.131	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
K/W	0.9349	likely_pathogenic	0.9469	pathogenic	-0.465	Destabilizing	1.0	D	0.734	prob.delet.	None	None	None	None	I
K/Y	0.8836	likely_pathogenic	0.9009	pathogenic	-0.062	Destabilizing	1.0	D	0.757	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.