TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	15875	47848;47849;47850	chr2:178617462;178617461;178617460	chr2:179482189;179482188;179482187
N2AB	14234	42925;42926;42927	chr2:178617462;178617461;178617460	chr2:179482189;179482188;179482187
N2A	13307	40144;40145;40146	chr2:178617462;178617461;178617460	chr2:179482189;179482188;179482187
N2B	6810	20653;20654;20655	chr2:178617462;178617461;178617460	chr2:179482189;179482188;179482187
Novex-1	6935	21028;21029;21030	chr2:178617462;178617461;178617460	chr2:179482189;179482188;179482187
Novex-2	7002	21229;21230;21231	chr2:178617462;178617461;178617460	chr2:179482189;179482188;179482187
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: S
• RefSeq wild type transcript codon: TCA
• RefSeq wild type template codon: AGT
• Domain: Fn3-3
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1254
• 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
S/P	rs1274510932	None	1.0	D	0.81	0.536	0.569101917167	gnomAD-3.1.2	6.59E-06	None	None	None	None	N	None	2.42E-05	0	0	0	0	None	0	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
S/A	0.1182	likely_benign	0.1451	benign	-0.37	Destabilizing	0.997	D	0.496	neutral	N	0.51753329	None	None	N
S/C	0.1743	likely_benign	0.1814	benign	-0.876	Destabilizing	1.0	D	0.785	deleterious	None	None	None	None	N
S/D	0.6135	likely_pathogenic	0.7068	pathogenic	-1.946	Destabilizing	0.999	D	0.617	neutral	None	None	None	None	N
S/E	0.6405	likely_pathogenic	0.6916	pathogenic	-1.903	Destabilizing	0.999	D	0.606	neutral	None	None	None	None	N
S/F	0.2588	likely_benign	0.3155	benign	-0.842	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
S/G	0.2058	likely_benign	0.2361	benign	-0.586	Destabilizing	0.999	D	0.539	neutral	None	None	None	None	N
S/H	0.4783	ambiguous	0.4861	ambiguous	-1.152	Destabilizing	1.0	D	0.8	deleterious	None	None	None	None	N
S/I	0.3985	ambiguous	0.4667	ambiguous	0.1	Stabilizing	1.0	D	0.807	deleterious	None	None	None	None	N
S/K	0.8625	likely_pathogenic	0.8801	pathogenic	-0.62	Destabilizing	0.999	D	0.613	neutral	None	None	None	None	N
S/L	0.1922	likely_benign	0.2267	benign	0.1	Stabilizing	1.0	D	0.755	deleterious	D	0.679342829	None	None	N
S/M	0.2907	likely_benign	0.3461	ambiguous	0.292	Stabilizing	1.0	D	0.798	deleterious	None	None	None	None	N
S/N	0.3112	likely_benign	0.3738	ambiguous	-1.115	Destabilizing	0.999	D	0.618	neutral	None	None	None	None	N
S/P	0.9745	likely_pathogenic	0.9826	pathogenic	-0.025	Destabilizing	1.0	D	0.81	deleterious	D	0.71688786	None	None	N
S/Q	0.6946	likely_pathogenic	0.7187	pathogenic	-1.332	Destabilizing	1.0	D	0.768	deleterious	None	None	None	None	N
S/R	0.7947	likely_pathogenic	0.8158	pathogenic	-0.473	Destabilizing	1.0	D	0.815	deleterious	None	None	None	None	N
S/T	0.0857	likely_benign	0.0968	benign	-0.803	Destabilizing	0.999	D	0.542	neutral	N	0.48522611	None	None	N
S/V	0.3358	likely_benign	0.3963	ambiguous	-0.025	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
S/W	0.4967	ambiguous	0.533	ambiguous	-1.024	Destabilizing	1.0	D	0.792	deleterious	None	None	None	None	N
S/Y	0.2584	likely_benign	0.3023	benign	-0.574	Destabilizing	1.0	D	0.821	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.