TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17060	51403;51404;51405	chr2:178610348;178610347;178610346	chr2:179475075;179475074;179475073
N2AB	15419	46480;46481;46482	chr2:178610348;178610347;178610346	chr2:179475075;179475074;179475073
N2A	14492	43699;43700;43701	chr2:178610348;178610347;178610346	chr2:179475075;179475074;179475073
N2B	7995	24208;24209;24210	chr2:178610348;178610347;178610346	chr2:179475075;179475074;179475073
Novex-1	8120	24583;24584;24585	chr2:178610348;178610347;178610346	chr2:179475075;179475074;179475073
Novex-2	8187	24784;24785;24786	chr2:178610348;178610347;178610346	chr2:179475075;179475074;179475073
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACC
• RefSeq wild type template codon: TGG
• Domain: Fn3-12
• Domain position: 14
• Structural Position: 16
• Q(SASA): 0.313
• 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
T/N	None	None	1.0	N	0.765	0.362	0.432041664125	gnomAD-4.0.0	1.5936E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.86277E-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
T/A	0.4014	ambiguous	0.399	ambiguous	-0.738	Destabilizing	0.999	D	0.509	neutral	D	0.539614957	None	None	N
T/C	0.7453	likely_pathogenic	0.741	pathogenic	-0.594	Destabilizing	1.0	D	0.685	prob.neutral	None	None	None	None	N
T/D	0.8163	likely_pathogenic	0.829	pathogenic	-1.019	Destabilizing	1.0	D	0.767	deleterious	None	None	None	None	N
T/E	0.8505	likely_pathogenic	0.8709	pathogenic	-1.019	Destabilizing	1.0	D	0.777	deleterious	None	None	None	None	N
T/F	0.8319	likely_pathogenic	0.8341	pathogenic	-0.992	Destabilizing	1.0	D	0.763	deleterious	None	None	None	None	N
T/G	0.3897	ambiguous	0.3816	ambiguous	-0.975	Destabilizing	1.0	D	0.724	prob.delet.	None	None	None	None	N
T/H	0.6479	likely_pathogenic	0.6731	pathogenic	-1.404	Destabilizing	1.0	D	0.702	prob.neutral	None	None	None	None	N
T/I	0.8341	likely_pathogenic	0.8713	pathogenic	-0.2	Destabilizing	1.0	D	0.757	deleterious	D	0.654594955	None	None	N
T/K	0.6715	likely_pathogenic	0.7026	pathogenic	-0.787	Destabilizing	1.0	D	0.775	deleterious	None	None	None	None	N
T/L	0.3983	ambiguous	0.4315	ambiguous	-0.2	Destabilizing	0.999	D	0.667	neutral	None	None	None	None	N
T/M	0.3351	likely_benign	0.356	ambiguous	0.254	Stabilizing	1.0	D	0.699	prob.neutral	None	None	None	None	N
T/N	0.3019	likely_benign	0.3288	benign	-0.892	Destabilizing	1.0	D	0.765	deleterious	N	0.46906868	None	None	N
T/P	0.9181	likely_pathogenic	0.9168	pathogenic	-0.349	Destabilizing	1.0	D	0.739	prob.delet.	D	0.677020553	None	None	N
T/Q	0.5455	ambiguous	0.5811	pathogenic	-1.149	Destabilizing	1.0	D	0.762	deleterious	None	None	None	None	N
T/R	0.6704	likely_pathogenic	0.676	pathogenic	-0.515	Destabilizing	1.0	D	0.748	deleterious	None	None	None	None	N
T/S	0.1697	likely_benign	0.1664	benign	-1.038	Destabilizing	0.999	D	0.539	neutral	N	0.483702079	None	None	N
T/V	0.6411	likely_pathogenic	0.6817	pathogenic	-0.349	Destabilizing	0.999	D	0.607	neutral	None	None	None	None	N
T/W	0.9615	likely_pathogenic	0.9632	pathogenic	-0.98	Destabilizing	1.0	D	0.695	prob.neutral	None	None	None	None	N
T/Y	0.8514	likely_pathogenic	0.8555	pathogenic	-0.686	Destabilizing	1.0	D	0.759	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.