TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35627	107104;107105;107106	chr2:178528872;178528871;178528870	chr2:179393599;179393598;179393597
N2AB	33986	102181;102182;102183	chr2:178528872;178528871;178528870	chr2:179393599;179393598;179393597
N2A	33059	99400;99401;99402	chr2:178528872;178528871;178528870	chr2:179393599;179393598;179393597
N2B	26562	79909;79910;79911	chr2:178528872;178528871;178528870	chr2:179393599;179393598;179393597
Novex-1	26687	80284;80285;80286	chr2:178528872;178528871;178528870	chr2:179393599;179393598;179393597
Novex-2	26754	80485;80486;80487	chr2:178528872;178528871;178528870	chr2:179393599;179393598;179393597
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-167
• Domain position: 21
• Structural Position: 31
• Q(SASA): 0.4201
• 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
K/R	rs1284079251	None	0.003	N	0.254	0.085	0.309530620856	gnomAD-3.1.2	6.57E-06	None	None	None	None	N	None	2.41E-05	0	0	0	0	None	0	0	0	0	0
K/R	rs1284079251	None	0.003	N	0.254	0.085	0.309530620856	gnomAD-4.0.0	6.56935E-06	None	None	None	None	N	None	2.41173E-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
K/A	0.7085	likely_pathogenic	0.7293	pathogenic	-0.396	Destabilizing	0.415	N	0.468	neutral	None	None	None	None	N
K/C	0.9379	likely_pathogenic	0.9397	pathogenic	-0.387	Destabilizing	0.996	D	0.695	prob.neutral	None	None	None	None	N
K/D	0.8695	likely_pathogenic	0.893	pathogenic	-0.093	Destabilizing	0.775	D	0.53	neutral	None	None	None	None	N
K/E	0.4007	ambiguous	0.4318	ambiguous	-0.039	Destabilizing	0.565	D	0.513	neutral	N	0.472643017	None	None	N
K/F	0.9428	likely_pathogenic	0.9518	pathogenic	-0.407	Destabilizing	0.987	D	0.693	prob.neutral	None	None	None	None	N
K/G	0.8234	likely_pathogenic	0.8461	pathogenic	-0.698	Destabilizing	0.775	D	0.555	neutral	None	None	None	None	N
K/H	0.5166	ambiguous	0.5228	ambiguous	-1.129	Destabilizing	0.961	D	0.633	neutral	None	None	None	None	N
K/I	0.6973	likely_pathogenic	0.721	pathogenic	0.351	Stabilizing	0.949	D	0.673	neutral	N	0.475763467	None	None	N
K/L	0.6986	likely_pathogenic	0.7199	pathogenic	0.351	Stabilizing	0.775	D	0.567	neutral	None	None	None	None	N
K/M	0.4924	ambiguous	0.5218	ambiguous	0.409	Stabilizing	0.996	D	0.631	neutral	None	None	None	None	N
K/N	0.6748	likely_pathogenic	0.7125	pathogenic	-0.143	Destabilizing	0.722	D	0.483	neutral	N	0.473683167	None	None	N
K/P	0.947	likely_pathogenic	0.9607	pathogenic	0.132	Stabilizing	0.961	D	0.595	neutral	None	None	None	None	N
K/Q	0.2493	likely_benign	0.2582	benign	-0.348	Destabilizing	0.722	D	0.535	neutral	N	0.474029883	None	None	N
K/R	0.1272	likely_benign	0.1288	benign	-0.364	Destabilizing	0.003	N	0.254	neutral	N	0.456137556	None	None	N
K/S	0.7128	likely_pathogenic	0.7439	pathogenic	-0.781	Destabilizing	0.118	N	0.383	neutral	None	None	None	None	N
K/T	0.3515	ambiguous	0.373	ambiguous	-0.542	Destabilizing	0.565	D	0.479	neutral	N	0.47333645	None	None	N
K/V	0.6865	likely_pathogenic	0.7036	pathogenic	0.132	Stabilizing	0.923	D	0.613	neutral	None	None	None	None	N
K/W	0.9487	likely_pathogenic	0.9532	pathogenic	-0.291	Destabilizing	0.996	D	0.699	prob.neutral	None	None	None	None	N
K/Y	0.8756	likely_pathogenic	0.8889	pathogenic	0.04	Stabilizing	0.987	D	0.672	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.