TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35344	106255;106256;106257	chr2:178530585;178530584;178530583	chr2:179395312;179395311;179395310
N2AB	33703	101332;101333;101334	chr2:178530585;178530584;178530583	chr2:179395312;179395311;179395310
N2A	32776	98551;98552;98553	chr2:178530585;178530584;178530583	chr2:179395312;179395311;179395310
N2B	26279	79060;79061;79062	chr2:178530585;178530584;178530583	chr2:179395312;179395311;179395310
Novex-1	26404	79435;79436;79437	chr2:178530585;178530584;178530583	chr2:179395312;179395311;179395310
Novex-2	26471	79636;79637;79638	chr2:178530585;178530584;178530583	chr2:179395312;179395311;179395310
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: L
• RefSeq wild type transcript codon: CTC
• RefSeq wild type template codon: GAG
• Domain: Ig-165
• Domain position: 59
• Structural Position: 138
• Q(SASA): 0.0522
• 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
L/H	None	None	1.0	D	0.913	0.892	0.932259407414	gnomAD-4.0.0	1.59088E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.8575E-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
L/A	0.944	likely_pathogenic	0.9324	pathogenic	-2.505	Highly Destabilizing	0.997	D	0.751	deleterious	None	None	None	None	N
L/C	0.9035	likely_pathogenic	0.8959	pathogenic	-1.658	Destabilizing	1.0	D	0.843	deleterious	None	None	None	None	N
L/D	0.9995	likely_pathogenic	0.9992	pathogenic	-3.301	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/E	0.9952	likely_pathogenic	0.9924	pathogenic	-2.98	Highly Destabilizing	1.0	D	0.903	deleterious	None	None	None	None	N
L/F	0.7414	likely_pathogenic	0.7069	pathogenic	-1.553	Destabilizing	1.0	D	0.781	deleterious	D	0.599218309	None	None	N
L/G	0.9822	likely_pathogenic	0.9755	pathogenic	-3.086	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/H	0.9924	likely_pathogenic	0.9879	pathogenic	-2.922	Highly Destabilizing	1.0	D	0.913	deleterious	D	0.641843729	None	None	N
L/I	0.3319	likely_benign	0.3182	benign	-0.745	Destabilizing	0.996	D	0.659	neutral	D	0.594180331	None	None	N
L/K	0.9929	likely_pathogenic	0.9875	pathogenic	-1.914	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
L/M	0.3208	likely_benign	0.302	benign	-0.974	Destabilizing	1.0	D	0.764	deleterious	None	None	None	None	N
L/N	0.9961	likely_pathogenic	0.994	pathogenic	-2.687	Highly Destabilizing	1.0	D	0.899	deleterious	None	None	None	None	N
L/P	0.9991	likely_pathogenic	0.9984	pathogenic	-1.326	Destabilizing	1.0	D	0.903	deleterious	D	0.641843729	None	None	N
L/Q	0.9833	likely_pathogenic	0.9734	pathogenic	-2.289	Highly Destabilizing	1.0	D	0.915	deleterious	None	None	None	None	N
L/R	0.9869	likely_pathogenic	0.9783	pathogenic	-2.135	Highly Destabilizing	0.999	D	0.9	deleterious	D	0.641641924	None	None	N
L/S	0.9951	likely_pathogenic	0.9926	pathogenic	-3.132	Highly Destabilizing	0.998	D	0.864	deleterious	None	None	None	None	N
L/T	0.9805	likely_pathogenic	0.9741	pathogenic	-2.647	Highly Destabilizing	0.91	D	0.565	neutral	None	None	None	None	N
L/V	0.4246	ambiguous	0.4045	ambiguous	-1.326	Destabilizing	0.996	D	0.683	prob.neutral	D	0.581198752	None	None	N
L/W	0.9713	likely_pathogenic	0.9539	pathogenic	-1.914	Destabilizing	1.0	D	0.894	deleterious	None	None	None	None	N
L/Y	0.9748	likely_pathogenic	0.9665	pathogenic	-1.726	Destabilizing	1.0	D	0.835	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.