TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	9000	27223;27224;27225	chr2:178713136;178713135;178713134	chr2:179577863;179577862;179577861
N2AB	8683	26272;26273;26274	chr2:178713136;178713135;178713134	chr2:179577863;179577862;179577861
N2A	7756	23491;23492;23493	chr2:178713136;178713135;178713134	chr2:179577863;179577862;179577861
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: A
• RefSeq wild type transcript codon: GCT
• RefSeq wild type template codon: CGA
• Domain: Ig-75
• Domain position: 75
• Structural Position: 158
• Q(SASA): 0.0729
• 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
A/V	rs752994608	None	0.79	N	0.399	0.527	0.672978241467	gnomAD-4.0.0	4.78971E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	6.29645E-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
A/C	0.9007	likely_pathogenic	0.9071	pathogenic	-1.836	Destabilizing	1.0	D	0.836	deleterious	None	None	None	None	N
A/D	0.9984	likely_pathogenic	0.9987	pathogenic	-2.791	Highly Destabilizing	1.0	D	0.875	deleterious	D	0.655252147	None	None	N
A/E	0.9958	likely_pathogenic	0.9968	pathogenic	-2.647	Highly Destabilizing	1.0	D	0.84	deleterious	None	None	None	None	N
A/F	0.9612	likely_pathogenic	0.9629	pathogenic	-1.011	Destabilizing	0.999	D	0.9	deleterious	None	None	None	None	N
A/G	0.5675	likely_pathogenic	0.5618	ambiguous	-1.78	Destabilizing	0.999	D	0.597	neutral	D	0.591931918	None	None	N
A/H	0.9975	likely_pathogenic	0.998	pathogenic	-1.833	Destabilizing	1.0	D	0.884	deleterious	None	None	None	None	N
A/I	0.7673	likely_pathogenic	0.787	pathogenic	-0.376	Destabilizing	0.988	D	0.747	deleterious	None	None	None	None	N
A/K	0.9986	likely_pathogenic	0.999	pathogenic	-1.43	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
A/L	0.7286	likely_pathogenic	0.7466	pathogenic	-0.376	Destabilizing	0.988	D	0.68	prob.neutral	None	None	None	None	N
A/M	0.8824	likely_pathogenic	0.8978	pathogenic	-0.802	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
A/N	0.9957	likely_pathogenic	0.9967	pathogenic	-1.724	Destabilizing	1.0	D	0.885	deleterious	None	None	None	None	N
A/P	0.9901	likely_pathogenic	0.9933	pathogenic	-0.676	Destabilizing	1.0	D	0.883	deleterious	D	0.617671834	None	None	N
A/Q	0.9913	likely_pathogenic	0.9929	pathogenic	-1.672	Destabilizing	1.0	D	0.883	deleterious	None	None	None	None	N
A/R	0.9931	likely_pathogenic	0.9941	pathogenic	-1.322	Destabilizing	1.0	D	0.877	deleterious	None	None	None	None	N
A/S	0.5168	ambiguous	0.5527	ambiguous	-2.099	Highly Destabilizing	0.996	D	0.613	neutral	D	0.617268226	None	None	N
A/T	0.6409	likely_pathogenic	0.6865	pathogenic	-1.848	Destabilizing	0.992	D	0.682	prob.neutral	D	0.638193405	None	None	N
A/V	0.4333	ambiguous	0.4532	ambiguous	-0.676	Destabilizing	0.79	D	0.399	neutral	N	0.502188693	None	None	N
A/W	0.9987	likely_pathogenic	0.9988	pathogenic	-1.579	Destabilizing	1.0	D	0.864	deleterious	None	None	None	None	N
A/Y	0.9942	likely_pathogenic	0.9949	pathogenic	-1.133	Destabilizing	1.0	D	0.907	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.