TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24836	74731;74732;74733	chr2:178571626;178571625;178571624	chr2:179436353;179436352;179436351
N2AB	23195	69808;69809;69810	chr2:178571626;178571625;178571624	chr2:179436353;179436352;179436351
N2A	22268	67027;67028;67029	chr2:178571626;178571625;178571624	chr2:179436353;179436352;179436351
N2B	15771	47536;47537;47538	chr2:178571626;178571625;178571624	chr2:179436353;179436352;179436351
Novex-1	15896	47911;47912;47913	chr2:178571626;178571625;178571624	chr2:179436353;179436352;179436351
Novex-2	15963	48112;48113;48114	chr2:178571626;178571625;178571624	chr2:179436353;179436352;179436351
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: D
• RefSeq wild type transcript codon: GAT
• RefSeq wild type template codon: CTA
• Domain: Fn3-68
• Domain position: 29
• Structural Position: 30
• Q(SASA): 0.4655
• 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
D/Y	rs759645630	-0.335	0.995	D	0.711	0.346	0.73550016056	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	5.62E-05	None	0	None	0	0	0
D/Y	rs759645630	-0.335	0.995	D	0.711	0.346	0.73550016056	gnomAD-4.0.0	1.59234E-06	None	None	None	None	N	None	0	0	None	0	2.7835E-05	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
D/A	0.5164	ambiguous	0.5471	ambiguous	-0.833	Destabilizing	0.811	D	0.623	neutral	N	0.48104325	None	None	N
D/C	0.8837	likely_pathogenic	0.8938	pathogenic	-0.263	Destabilizing	0.999	D	0.722	prob.delet.	None	None	None	None	N
D/E	0.5063	ambiguous	0.4876	ambiguous	-0.679	Destabilizing	0.103	N	0.178	neutral	N	0.471964669	None	None	N
D/F	0.9224	likely_pathogenic	0.9294	pathogenic	-0.639	Destabilizing	0.988	D	0.709	prob.delet.	None	None	None	None	N
D/G	0.5513	ambiguous	0.5569	ambiguous	-1.143	Destabilizing	0.896	D	0.599	neutral	N	0.511201827	None	None	N
D/H	0.7038	likely_pathogenic	0.7161	pathogenic	-0.948	Destabilizing	0.996	D	0.635	neutral	N	0.48904542	None	None	N
D/I	0.7904	likely_pathogenic	0.8202	pathogenic	-0.019	Destabilizing	0.976	D	0.721	prob.delet.	None	None	None	None	N
D/K	0.8144	likely_pathogenic	0.8199	pathogenic	-0.3	Destabilizing	0.851	D	0.601	neutral	None	None	None	None	N
D/L	0.7727	likely_pathogenic	0.7992	pathogenic	-0.019	Destabilizing	0.952	D	0.647	neutral	None	None	None	None	N
D/M	0.8892	likely_pathogenic	0.9023	pathogenic	0.52	Stabilizing	0.999	D	0.691	prob.neutral	None	None	None	None	N
D/N	0.1557	likely_benign	0.1743	benign	-0.705	Destabilizing	0.896	D	0.561	neutral	N	0.502840133	None	None	N
D/P	0.9226	likely_pathogenic	0.9335	pathogenic	-0.267	Destabilizing	0.988	D	0.635	neutral	None	None	None	None	N
D/Q	0.7561	likely_pathogenic	0.7649	pathogenic	-0.61	Destabilizing	0.507	D	0.242	neutral	None	None	None	None	N
D/R	0.8192	likely_pathogenic	0.8268	pathogenic	-0.244	Destabilizing	0.976	D	0.69	prob.neutral	None	None	None	None	N
D/S	0.2496	likely_benign	0.2594	benign	-0.944	Destabilizing	0.851	D	0.551	neutral	None	None	None	None	N
D/T	0.3283	likely_benign	0.3385	benign	-0.68	Destabilizing	0.261	N	0.271	neutral	None	None	None	None	N
D/V	0.5991	likely_pathogenic	0.6312	pathogenic	-0.267	Destabilizing	0.938	D	0.642	neutral	N	0.498413489	None	None	N
D/W	0.9853	likely_pathogenic	0.9869	pathogenic	-0.435	Destabilizing	0.999	D	0.707	prob.neutral	None	None	None	None	N
D/Y	0.6741	likely_pathogenic	0.6955	pathogenic	-0.386	Destabilizing	0.995	D	0.711	prob.delet.	D	0.529141498	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.