TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22523	67792;67793;67794	chr2:178579630;178579629;178579628	chr2:179444357;179444356;179444355
N2AB	20882	62869;62870;62871	chr2:178579630;178579629;178579628	chr2:179444357;179444356;179444355
N2A	19955	60088;60089;60090	chr2:178579630;178579629;178579628	chr2:179444357;179444356;179444355
N2B	13458	40597;40598;40599	chr2:178579630;178579629;178579628	chr2:179444357;179444356;179444355
Novex-1	13583	40972;40973;40974	chr2:178579630;178579629;178579628	chr2:179444357;179444356;179444355
Novex-2	13650	41173;41174;41175	chr2:178579630;178579629;178579628	chr2:179444357;179444356;179444355
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-51
• Domain position: 73
• Structural Position: 108
• Q(SASA): 0.064
• 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
V/G	rs1274914285	-3.267	1.0	D	0.891	0.831	0.94499076129	gnomAD-2.1.1	4.03E-06	None	None	None	None	N	None	0	2.9E-05	None	0	0	None	0	None	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
V/A	0.7607	likely_pathogenic	0.846	pathogenic	-2.337	Highly Destabilizing	0.998	D	0.665	neutral	D	0.53931271	None	None	N
V/C	0.9455	likely_pathogenic	0.9623	pathogenic	-2.02	Highly Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
V/D	0.9976	likely_pathogenic	0.9984	pathogenic	-3.313	Highly Destabilizing	1.0	D	0.9	deleterious	None	None	None	None	N
V/E	0.993	likely_pathogenic	0.9952	pathogenic	-3.023	Highly Destabilizing	1.0	D	0.876	deleterious	D	0.62669769	None	None	N
V/F	0.877	likely_pathogenic	0.9246	pathogenic	-1.33	Destabilizing	1.0	D	0.826	deleterious	None	None	None	None	N
V/G	0.8835	likely_pathogenic	0.9315	pathogenic	-2.944	Highly Destabilizing	1.0	D	0.891	deleterious	D	0.62669769	None	None	N
V/H	0.9978	likely_pathogenic	0.9987	pathogenic	-2.822	Highly Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
V/I	0.122	likely_benign	0.1297	benign	-0.592	Destabilizing	0.813	D	0.323	neutral	None	None	None	None	N
V/K	0.9942	likely_pathogenic	0.9957	pathogenic	-1.999	Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/L	0.7353	likely_pathogenic	0.7965	pathogenic	-0.592	Destabilizing	0.981	D	0.609	neutral	D	0.523735988	None	None	N
V/M	0.8066	likely_pathogenic	0.8676	pathogenic	-0.833	Destabilizing	0.999	D	0.78	deleterious	D	0.547959991	None	None	N
V/N	0.9926	likely_pathogenic	0.9949	pathogenic	-2.558	Highly Destabilizing	1.0	D	0.918	deleterious	None	None	None	None	N
V/P	0.9964	likely_pathogenic	0.9967	pathogenic	-1.151	Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
V/Q	0.9913	likely_pathogenic	0.9944	pathogenic	-2.271	Highly Destabilizing	1.0	D	0.913	deleterious	None	None	None	None	N
V/R	0.9869	likely_pathogenic	0.9908	pathogenic	-1.979	Destabilizing	1.0	D	0.92	deleterious	None	None	None	None	N
V/S	0.9563	likely_pathogenic	0.9734	pathogenic	-3.142	Highly Destabilizing	1.0	D	0.878	deleterious	None	None	None	None	N
V/T	0.9131	likely_pathogenic	0.9356	pathogenic	-2.692	Highly Destabilizing	0.998	D	0.717	prob.delet.	None	None	None	None	N
V/W	0.9984	likely_pathogenic	0.9992	pathogenic	-1.944	Destabilizing	1.0	D	0.874	deleterious	None	None	None	None	N
V/Y	0.9886	likely_pathogenic	0.9936	pathogenic	-1.579	Destabilizing	1.0	D	0.837	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.