TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	8769	26530;26531;26532	chr2:178714469;178714468;178714467	chr2:179579196;179579195;179579194
N2AB	8452	25579;25580;25581	chr2:178714469;178714468;178714467	chr2:179579196;179579195;179579194
N2A	7525	22798;22799;22800	chr2:178714469;178714468;178714467	chr2:179579196;179579195;179579194
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: W
• RefSeq wild type transcript codon: TGG
• RefSeq wild type template codon: ACC
• Domain: Ig-73
• Domain position: 34
• Structural Position: 48
• Q(SASA): 0.1228
• 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
W/G	rs779847107	-2.495	1.0	D	0.817	0.916	0.929467472191	gnomAD-4.0.0	4.7901E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29681E-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
W/A	0.9676	likely_pathogenic	0.9835	pathogenic	-2.735	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
W/C	0.9704	likely_pathogenic	0.9864	pathogenic	-1.577	Destabilizing	1.0	D	0.786	deleterious	D	0.690064231	None	None	N
W/D	0.9981	likely_pathogenic	0.9989	pathogenic	-3.24	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
W/E	0.9975	likely_pathogenic	0.9986	pathogenic	-3.113	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
W/F	0.4925	ambiguous	0.5382	ambiguous	-1.642	Destabilizing	1.0	D	0.811	deleterious	None	None	None	None	N
W/G	0.9255	likely_pathogenic	0.9572	pathogenic	-2.984	Highly Destabilizing	1.0	D	0.817	deleterious	D	0.705881788	None	None	N
W/H	0.9893	likely_pathogenic	0.9931	pathogenic	-2.111	Highly Destabilizing	1.0	D	0.819	deleterious	None	None	None	None	N
W/I	0.8629	likely_pathogenic	0.9169	pathogenic	-1.791	Destabilizing	1.0	D	0.85	deleterious	None	None	None	None	N
W/K	0.9986	likely_pathogenic	0.9993	pathogenic	-2.402	Highly Destabilizing	1.0	D	0.833	deleterious	None	None	None	None	N
W/L	0.7214	likely_pathogenic	0.8166	pathogenic	-1.791	Destabilizing	1.0	D	0.817	deleterious	D	0.705881788	None	None	N
W/M	0.9477	likely_pathogenic	0.9724	pathogenic	-1.333	Destabilizing	1.0	D	0.778	deleterious	None	None	None	None	N
W/N	0.9958	likely_pathogenic	0.9977	pathogenic	-3.172	Highly Destabilizing	1.0	D	0.865	deleterious	None	None	None	None	N
W/P	0.9944	likely_pathogenic	0.9967	pathogenic	-2.134	Highly Destabilizing	1.0	D	0.867	deleterious	None	None	None	None	N
W/Q	0.9975	likely_pathogenic	0.9988	pathogenic	-2.938	Highly Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
W/R	0.996	likely_pathogenic	0.9977	pathogenic	-2.31	Highly Destabilizing	1.0	D	0.861	deleterious	D	0.706083592	None	None	N
W/S	0.9588	likely_pathogenic	0.9779	pathogenic	-3.276	Highly Destabilizing	1.0	D	0.84	deleterious	D	0.706083592	None	None	N
W/T	0.9706	likely_pathogenic	0.9848	pathogenic	-3.074	Highly Destabilizing	1.0	D	0.822	deleterious	None	None	None	None	N
W/V	0.884	likely_pathogenic	0.9351	pathogenic	-2.134	Highly Destabilizing	1.0	D	0.837	deleterious	None	None	None	None	N
W/Y	0.8159	likely_pathogenic	0.8558	pathogenic	-1.494	Destabilizing	1.0	D	0.782	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.