TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	21372	64339;64340;64341	chr2:178586787;178586786;178586785	chr2:179451514;179451513;179451512
N2AB	19731	59416;59417;59418	chr2:178586787;178586786;178586785	chr2:179451514;179451513;179451512
N2A	18804	56635;56636;56637	chr2:178586787;178586786;178586785	chr2:179451514;179451513;179451512
N2B	12307	37144;37145;37146	chr2:178586787;178586786;178586785	chr2:179451514;179451513;179451512
Novex-1	12432	37519;37520;37521	chr2:178586787;178586786;178586785	chr2:179451514;179451513;179451512
Novex-2	12499	37720;37721;37722	chr2:178586787;178586786;178586785	chr2:179451514;179451513;179451512
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: Fn3-43
• Domain position: 7
• Structural Position: 7
• Q(SASA): 0.601
• 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/I	None	None	1.0	N	0.73	0.43	0.601896402847	gnomAD-4.0.0	6.84762E-07	None	None	None	None	I	None	0	0	None	0	0	None	0	0	8.99912E-07	0	0
K/R	rs1186477441	-0.089	0.999	N	0.596	0.146	0.287603790349	gnomAD-2.1.1	3.19E-05	None	None	None	None	I	None	0	0	None	0	0	None	0	None	0	6.48E-05	0
K/R	rs1186477441	-0.089	0.999	N	0.596	0.146	0.287603790349	gnomAD-4.0.0	1.36952E-06	None	None	None	None	I	None	0	0	None	0	0	None	0	0	1.79982E-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	0.814	likely_pathogenic	0.6472	pathogenic	0.002	Stabilizing	0.999	D	0.696	prob.neutral	None	None	None	None	I
K/C	0.898	likely_pathogenic	0.8032	pathogenic	-0.219	Destabilizing	1.0	D	0.744	deleterious	None	None	None	None	I
K/D	0.8639	likely_pathogenic	0.7366	pathogenic	0.079	Stabilizing	1.0	D	0.748	deleterious	None	None	None	None	I
K/E	0.7103	likely_pathogenic	0.4887	ambiguous	0.112	Stabilizing	0.999	D	0.619	neutral	N	0.507955164	None	None	I
K/F	0.9406	likely_pathogenic	0.8799	pathogenic	-0.055	Destabilizing	1.0	D	0.705	prob.neutral	None	None	None	None	I
K/G	0.8102	likely_pathogenic	0.6582	pathogenic	-0.237	Destabilizing	1.0	D	0.675	neutral	None	None	None	None	I
K/H	0.4955	ambiguous	0.393	ambiguous	-0.464	Destabilizing	1.0	D	0.677	prob.neutral	None	None	None	None	I
K/I	0.8059	likely_pathogenic	0.6626	pathogenic	0.562	Stabilizing	1.0	D	0.73	prob.delet.	N	0.473495152	None	None	I
K/L	0.7481	likely_pathogenic	0.5985	pathogenic	0.562	Stabilizing	1.0	D	0.675	neutral	None	None	None	None	I
K/M	0.6144	likely_pathogenic	0.4488	ambiguous	0.209	Stabilizing	1.0	D	0.669	neutral	None	None	None	None	I
K/N	0.7483	likely_pathogenic	0.5985	pathogenic	0.149	Stabilizing	1.0	D	0.714	prob.delet.	N	0.436492136	None	None	I
K/P	0.9612	likely_pathogenic	0.9302	pathogenic	0.404	Stabilizing	1.0	D	0.739	prob.delet.	None	None	None	None	I
K/Q	0.361	ambiguous	0.2301	benign	0.032	Stabilizing	1.0	D	0.69	prob.neutral	N	0.492062992	None	None	I
K/R	0.1295	likely_benign	0.1115	benign	-0.104	Destabilizing	0.999	D	0.596	neutral	N	0.489273403	None	None	I
K/S	0.828	likely_pathogenic	0.6657	pathogenic	-0.331	Destabilizing	0.999	D	0.687	prob.neutral	None	None	None	None	I
K/T	0.6724	likely_pathogenic	0.4964	ambiguous	-0.138	Destabilizing	1.0	D	0.725	prob.delet.	N	0.494911296	None	None	I
K/V	0.765	likely_pathogenic	0.6079	pathogenic	0.404	Stabilizing	1.0	D	0.727	prob.delet.	None	None	None	None	I
K/W	0.9325	likely_pathogenic	0.8784	pathogenic	-0.074	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	I
K/Y	0.8278	likely_pathogenic	0.7215	pathogenic	0.261	Stabilizing	1.0	D	0.725	prob.delet.	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.