TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	33437	100534;100535;100536	chr2:178536438;178536437;178536436	chr2:179401165;179401164;179401163
N2AB	31796	95611;95612;95613	chr2:178536438;178536437;178536436	chr2:179401165;179401164;179401163
N2A	30869	92830;92831;92832	chr2:178536438;178536437;178536436	chr2:179401165;179401164;179401163
N2B	24372	73339;73340;73341	chr2:178536438;178536437;178536436	chr2:179401165;179401164;179401163
Novex-1	24497	73714;73715;73716	chr2:178536438;178536437;178536436	chr2:179401165;179401164;179401163
Novex-2	24564	73915;73916;73917	chr2:178536438;178536437;178536436	chr2:179401165;179401164;179401163
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: N
• RefSeq wild type transcript codon: AAT
• RefSeq wild type template codon: TTA
• Domain: Fn3-131
• Domain position: 46
• Structural Position: 63
• Q(SASA): 0.8781
• 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
N/S	rs1691532335	None	0.925	N	0.537	0.22	0.176091768786	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
N/S	rs1691532335	None	0.925	N	0.537	0.22	0.176091768786	gnomAD-4.0.0	8.98166E-06	None	None	None	None	N	None	3.38868E-05	0	None	0	0	None	0	1.12309E-03	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
N/A	0.3106	likely_benign	0.2839	benign	-0.134	Destabilizing	0.942	D	0.518	neutral	None	None	None	None	N
N/C	0.4248	ambiguous	0.3713	ambiguous	0.12	Stabilizing	1.0	D	0.66	neutral	None	None	None	None	N
N/D	0.1693	likely_benign	0.158	benign	0.245	Stabilizing	0.98	D	0.516	neutral	N	0.449603081	None	None	N
N/E	0.3643	ambiguous	0.3398	benign	0.202	Stabilizing	0.985	D	0.527	neutral	None	None	None	None	N
N/F	0.7192	likely_pathogenic	0.6783	pathogenic	-0.703	Destabilizing	0.999	D	0.635	neutral	None	None	None	None	N
N/G	0.2651	likely_benign	0.2263	benign	-0.251	Destabilizing	0.092	N	0.302	neutral	None	None	None	None	N
N/H	0.1913	likely_benign	0.173	benign	-0.214	Destabilizing	0.998	D	0.59	neutral	N	0.493316572	None	None	N
N/I	0.3505	ambiguous	0.3559	ambiguous	0.075	Stabilizing	0.989	D	0.629	neutral	N	0.485331807	None	None	N
N/K	0.312	likely_benign	0.309	benign	0.155	Stabilizing	0.98	D	0.522	neutral	N	0.419106815	None	None	N
N/L	0.3362	likely_benign	0.3164	benign	0.075	Stabilizing	0.991	D	0.558	neutral	None	None	None	None	N
N/M	0.4338	ambiguous	0.3864	ambiguous	0.038	Stabilizing	1.0	D	0.64	neutral	None	None	None	None	N
N/P	0.6098	likely_pathogenic	0.6478	pathogenic	0.03	Stabilizing	0.999	D	0.615	neutral	None	None	None	None	N
N/Q	0.3422	ambiguous	0.3029	benign	-0.216	Destabilizing	0.999	D	0.577	neutral	None	None	None	None	N
N/R	0.4197	ambiguous	0.4061	ambiguous	0.222	Stabilizing	0.996	D	0.586	neutral	None	None	None	None	N
N/S	0.1198	likely_benign	0.115	benign	-0.049	Destabilizing	0.925	D	0.537	neutral	N	0.408697821	None	None	N
N/T	0.2173	likely_benign	0.2113	benign	0.036	Stabilizing	0.248	N	0.438	neutral	N	0.439135371	None	None	N
N/V	0.37	ambiguous	0.3656	ambiguous	0.03	Stabilizing	0.991	D	0.581	neutral	None	None	None	None	N
N/W	0.859	likely_pathogenic	0.8305	pathogenic	-0.817	Destabilizing	1.0	D	0.683	prob.neutral	None	None	None	None	N
N/Y	0.2634	likely_benign	0.2542	benign	-0.484	Destabilizing	0.998	D	0.631	neutral	N	0.504013569	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.