TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9981	30166;30167;30168	chr2:178704531;178704530;178704529	chr2:179569258;179569257;179569256
N2AB	9664	29215;29216;29217	chr2:178704531;178704530;178704529	chr2:179569258;179569257;179569256
N2A	8737	26434;26435;26436	chr2:178704531;178704530;178704529	chr2:179569258;179569257;179569256
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: S
• RefSeq wild type transcript codon: AGC
• RefSeq wild type template codon: TCG
• Domain: Ig-84
• Domain position: 82
• Structural Position: 171
• Q(SASA): 0.2562
• 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/N	None	None	0.939	None	0.545	0.282	0.149567049428	gnomAD-4.0.0	3.60097E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	3.93751E-06	0	0
S/T	None	None	0.969	None	0.479	0.263	0.134241683229	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	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	0.3172	likely_benign	0.2708	benign	-0.506	Destabilizing	0.807	D	0.367	neutral	None	None	None	None	N
S/C	0.6758	likely_pathogenic	0.6399	pathogenic	-0.357	Destabilizing	0.999	D	0.661	neutral	None	None	None	None	N
S/D	0.968	likely_pathogenic	0.9498	pathogenic	-0.081	Destabilizing	0.976	D	0.531	neutral	None	None	None	None	N
S/E	0.9733	likely_pathogenic	0.9519	pathogenic	-0.146	Destabilizing	0.976	D	0.537	neutral	None	None	None	None	N
S/F	0.9214	likely_pathogenic	0.8513	pathogenic	-0.896	Destabilizing	0.998	D	0.693	prob.neutral	None	None	None	None	N
S/G	0.4574	ambiguous	0.3926	ambiguous	-0.678	Destabilizing	0.02	N	0.219	neutral	None	None	None	None	N
S/H	0.9193	likely_pathogenic	0.8824	pathogenic	-1.193	Destabilizing	0.999	D	0.652	neutral	None	None	None	None	N
S/I	0.8444	likely_pathogenic	0.7783	pathogenic	-0.171	Destabilizing	0.997	D	0.686	prob.neutral	None	None	None	None	N
S/K	0.9928	likely_pathogenic	0.9862	pathogenic	-0.645	Destabilizing	0.976	D	0.55	neutral	None	None	None	None	N
S/L	0.7433	likely_pathogenic	0.6135	pathogenic	-0.171	Destabilizing	0.993	D	0.655	neutral	None	None	None	None	N
S/M	0.7805	likely_pathogenic	0.7106	pathogenic	0.12	Stabilizing	0.999	D	0.659	neutral	None	None	None	None	N
S/N	0.6179	likely_pathogenic	0.5887	pathogenic	-0.407	Destabilizing	0.939	D	0.545	neutral	None	None	None	None	N
S/P	0.9802	likely_pathogenic	0.9674	pathogenic	-0.251	Destabilizing	0.998	D	0.692	prob.neutral	None	None	None	None	N
S/Q	0.947	likely_pathogenic	0.9222	pathogenic	-0.662	Destabilizing	0.998	D	0.626	neutral	None	None	None	None	N
S/R	0.9856	likely_pathogenic	0.9715	pathogenic	-0.43	Destabilizing	0.996	D	0.684	prob.neutral	None	None	None	None	N
S/T	0.3818	ambiguous	0.31	benign	-0.488	Destabilizing	0.969	D	0.479	neutral	None	None	None	None	N
S/V	0.8032	likely_pathogenic	0.7431	pathogenic	-0.251	Destabilizing	0.993	D	0.676	prob.neutral	None	None	None	None	N
S/W	0.939	likely_pathogenic	0.902	pathogenic	-0.864	Destabilizing	0.999	D	0.697	prob.neutral	None	None	None	None	N
S/Y	0.8682	likely_pathogenic	0.7952	pathogenic	-0.609	Destabilizing	0.998	D	0.693	prob.neutral	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.