TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22832	68719;68720;68721	chr2:178578021;178578020;178578019	chr2:179442748;179442747;179442746
N2AB	21191	63796;63797;63798	chr2:178578021;178578020;178578019	chr2:179442748;179442747;179442746
N2A	20264	61015;61016;61017	chr2:178578021;178578020;178578019	chr2:179442748;179442747;179442746
N2B	13767	41524;41525;41526	chr2:178578021;178578020;178578019	chr2:179442748;179442747;179442746
Novex-1	13892	41899;41900;41901	chr2:178578021;178578020;178578019	chr2:179442748;179442747;179442746
Novex-2	13959	42100;42101;42102	chr2:178578021;178578020;178578019	chr2:179442748;179442747;179442746
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-53
• Domain position: 90
• Structural Position: 123
• Q(SASA): 0.1939
• 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
P/S	None	None	0.851	N	0.641	0.209	0.27479166964	gnomAD-4.0.0	1.36896E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.99703E-07	1.16007E-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
P/A	0.088	likely_benign	0.0836	benign	-1.695	Destabilizing	0.824	D	0.589	neutral	N	0.481960641	None	None	N
P/C	0.5497	ambiguous	0.529	ambiguous	-1.052	Destabilizing	0.999	D	0.829	deleterious	None	None	None	None	N
P/D	0.8743	likely_pathogenic	0.8681	pathogenic	-1.4	Destabilizing	0.991	D	0.643	neutral	None	None	None	None	N
P/E	0.6685	likely_pathogenic	0.6467	pathogenic	-1.368	Destabilizing	0.968	D	0.636	neutral	None	None	None	None	N
P/F	0.7383	likely_pathogenic	0.7057	pathogenic	-1.272	Destabilizing	0.991	D	0.82	deleterious	None	None	None	None	N
P/G	0.5176	ambiguous	0.4804	ambiguous	-2.047	Highly Destabilizing	0.968	D	0.655	prob.neutral	None	None	None	None	N
P/H	0.4815	ambiguous	0.4495	ambiguous	-1.546	Destabilizing	0.999	D	0.751	deleterious	None	None	None	None	N
P/I	0.3775	ambiguous	0.3758	ambiguous	-0.811	Destabilizing	0.883	D	0.73	deleterious	None	None	None	None	N
P/K	0.6968	likely_pathogenic	0.6671	pathogenic	-1.258	Destabilizing	0.938	D	0.637	neutral	None	None	None	None	N
P/L	0.2262	likely_benign	0.2158	benign	-0.811	Destabilizing	0.851	D	0.69	prob.delet.	N	0.463781007	None	None	N
P/M	0.4887	ambiguous	0.4609	ambiguous	-0.607	Destabilizing	0.991	D	0.75	deleterious	None	None	None	None	N
P/N	0.6613	likely_pathogenic	0.642	pathogenic	-1.08	Destabilizing	0.991	D	0.633	neutral	None	None	None	None	N
P/Q	0.3813	ambiguous	0.3457	ambiguous	-1.223	Destabilizing	0.996	D	0.69	prob.delet.	N	0.501448002	None	None	N
P/R	0.5283	ambiguous	0.4934	ambiguous	-0.774	Destabilizing	0.988	D	0.712	prob.delet.	N	0.509588303	None	None	N
P/S	0.2091	likely_benign	0.1895	benign	-1.668	Destabilizing	0.851	D	0.641	neutral	N	0.473682508	None	None	N
P/T	0.1778	likely_benign	0.1716	benign	-1.523	Destabilizing	0.132	N	0.421	neutral	N	0.511859474	None	None	N
P/V	0.2373	likely_benign	0.2395	benign	-1.072	Destabilizing	0.078	N	0.511	neutral	None	None	None	None	N
P/W	0.8872	likely_pathogenic	0.8663	pathogenic	-1.476	Destabilizing	0.999	D	0.824	deleterious	None	None	None	None	N
P/Y	0.7641	likely_pathogenic	0.7446	pathogenic	-1.182	Destabilizing	0.997	D	0.817	deleterious	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.