TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24308	73147;73148;73149	chr2:178573210;178573209;178573208	chr2:179437937;179437936;179437935
N2AB	22667	68224;68225;68226	chr2:178573210;178573209;178573208	chr2:179437937;179437936;179437935
N2A	21740	65443;65444;65445	chr2:178573210;178573209;178573208	chr2:179437937;179437936;179437935
N2B	15243	45952;45953;45954	chr2:178573210;178573209;178573208	chr2:179437937;179437936;179437935
Novex-1	15368	46327;46328;46329	chr2:178573210;178573209;178573208	chr2:179437937;179437936;179437935
Novex-2	15435	46528;46529;46530	chr2:178573210;178573209;178573208	chr2:179437937;179437936;179437935
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: P
• RefSeq wild type transcript codon: CCA
• RefSeq wild type template codon: GGT
• Domain: Fn3-64
• Domain position: 87
• Structural Position: 120
• Q(SASA): 0.3687
• 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
P/A	rs1334601287	-1.254	0.955	N	0.622	0.341	0.227934060464	gnomAD-2.1.1	4.1E-06	None	None	None	None	N	None	0	2.93E-05	None	0	0	None	0	None	0	0	0
P/A	rs1334601287	-1.254	0.955	N	0.622	0.341	0.227934060464	gnomAD-4.0.0	1.60722E-06	None	None	None	None	N	None	0	2.30394E-05	None	0	0	None	0	0	0	0	0
P/R	rs1553608507	None	0.993	D	0.857	0.481	0.619820317479	gnomAD-4.0.0	1.37444E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	1.7452E-04	9.02646E-07	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
P/A	0.0676	likely_benign	0.0677	benign	-1.403	Destabilizing	0.955	D	0.622	neutral	N	0.465706791	None	None	N
P/C	0.4439	ambiguous	0.4586	ambiguous	-0.754	Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
P/D	0.8499	likely_pathogenic	0.8019	pathogenic	-1.343	Destabilizing	0.995	D	0.801	deleterious	None	None	None	None	N
P/E	0.6178	likely_pathogenic	0.5326	ambiguous	-1.413	Destabilizing	0.995	D	0.783	deleterious	None	None	None	None	N
P/F	0.4799	ambiguous	0.4573	ambiguous	-1.321	Destabilizing	0.999	D	0.883	deleterious	None	None	None	None	N
P/G	0.4535	ambiguous	0.47	ambiguous	-1.641	Destabilizing	0.995	D	0.751	deleterious	None	None	None	None	N
P/H	0.3849	ambiguous	0.3418	ambiguous	-1.17	Destabilizing	1.0	D	0.854	deleterious	None	None	None	None	N
P/I	0.3516	ambiguous	0.3441	ambiguous	-0.872	Destabilizing	0.995	D	0.868	deleterious	None	None	None	None	N
P/K	0.6731	likely_pathogenic	0.5778	pathogenic	-1.102	Destabilizing	0.995	D	0.799	deleterious	None	None	None	None	N
P/L	0.187	likely_benign	0.1655	benign	-0.872	Destabilizing	0.987	D	0.798	deleterious	N	0.5140813	None	None	N
P/M	0.3802	ambiguous	0.3746	ambiguous	-0.511	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
P/N	0.6406	likely_pathogenic	0.5929	pathogenic	-0.762	Destabilizing	0.995	D	0.835	deleterious	None	None	None	None	N
P/Q	0.3439	ambiguous	0.2855	benign	-1.058	Destabilizing	0.997	D	0.839	deleterious	D	0.527465522	None	None	N
P/R	0.492	ambiguous	0.3994	ambiguous	-0.465	Destabilizing	0.993	D	0.857	deleterious	D	0.531731483	None	None	N
P/S	0.1755	likely_benign	0.1681	benign	-1.179	Destabilizing	0.987	D	0.728	prob.delet.	N	0.513120249	None	None	N
P/T	0.1798	likely_benign	0.1671	benign	-1.159	Destabilizing	0.235	N	0.428	neutral	D	0.527212032	None	None	N
P/V	0.2156	likely_benign	0.2149	benign	-1.015	Destabilizing	0.99	D	0.748	deleterious	None	None	None	None	N
P/W	0.7495	likely_pathogenic	0.7478	pathogenic	-1.42	Destabilizing	1.0	D	0.849	deleterious	None	None	None	None	N
P/Y	0.5335	ambiguous	0.506	ambiguous	-1.171	Destabilizing	1.0	D	0.883	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.