TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35677	107254;107255;107256	chr2:178528722;178528721;178528720	chr2:179393449;179393448;179393447
N2AB	34036	102331;102332;102333	chr2:178528722;178528721;178528720	chr2:179393449;179393448;179393447
N2A	33109	99550;99551;99552	chr2:178528722;178528721;178528720	chr2:179393449;179393448;179393447
N2B	26612	80059;80060;80061	chr2:178528722;178528721;178528720	chr2:179393449;179393448;179393447
Novex-1	26737	80434;80435;80436	chr2:178528722;178528721;178528720	chr2:179393449;179393448;179393447
Novex-2	26804	80635;80636;80637	chr2:178528722;178528721;178528720	chr2:179393449;179393448;179393447
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: C
• RefSeq wild type transcript codon: TGC
• RefSeq wild type template codon: ACG
• Domain: Ig-167
• Domain position: 71
• Structural Position: 156
• Q(SASA): 0.0898
• 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
C/R	None	None	0.997	N	0.862	0.591	0.801889373885	gnomAD-4.0.0	3.42172E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	4.49788E-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
C/A	0.8715	likely_pathogenic	0.8791	pathogenic	-1.725	Destabilizing	0.931	D	0.641	neutral	None	None	None	None	N
C/D	0.9985	likely_pathogenic	0.9986	pathogenic	-1.626	Destabilizing	0.996	D	0.857	deleterious	None	None	None	None	N
C/E	0.999	likely_pathogenic	0.9991	pathogenic	-1.381	Destabilizing	0.996	D	0.861	deleterious	None	None	None	None	N
C/F	0.7204	likely_pathogenic	0.7242	pathogenic	-1.034	Destabilizing	0.999	D	0.846	deleterious	N	0.480067634	None	None	N
C/G	0.7925	likely_pathogenic	0.8169	pathogenic	-2.094	Highly Destabilizing	0.98	D	0.841	deleterious	N	0.481107784	None	None	N
C/H	0.9926	likely_pathogenic	0.993	pathogenic	-2.293	Highly Destabilizing	1.0	D	0.866	deleterious	None	None	None	None	N
C/I	0.8601	likely_pathogenic	0.8646	pathogenic	-0.719	Destabilizing	0.998	D	0.789	deleterious	None	None	None	None	N
C/K	0.9987	likely_pathogenic	0.9988	pathogenic	-1.26	Destabilizing	0.996	D	0.851	deleterious	None	None	None	None	N
C/L	0.7888	likely_pathogenic	0.7761	pathogenic	-0.719	Destabilizing	0.993	D	0.752	deleterious	None	None	None	None	N
C/M	0.9329	likely_pathogenic	0.9354	pathogenic	0.043	Stabilizing	1.0	D	0.758	deleterious	None	None	None	None	N
C/N	0.9914	likely_pathogenic	0.9921	pathogenic	-1.882	Destabilizing	0.996	D	0.863	deleterious	None	None	None	None	N
C/P	0.9982	likely_pathogenic	0.9985	pathogenic	-1.032	Destabilizing	0.998	D	0.865	deleterious	None	None	None	None	N
C/Q	0.9966	likely_pathogenic	0.997	pathogenic	-1.383	Destabilizing	0.998	D	0.863	deleterious	None	None	None	None	N
C/R	0.9869	likely_pathogenic	0.9881	pathogenic	-1.683	Destabilizing	0.997	D	0.862	deleterious	N	0.481107784	None	None	N
C/S	0.9371	likely_pathogenic	0.944	pathogenic	-2.186	Highly Destabilizing	0.659	D	0.603	neutral	N	0.481107784	None	None	N
C/T	0.9631	likely_pathogenic	0.9657	pathogenic	-1.753	Destabilizing	0.971	D	0.751	deleterious	None	None	None	None	N
C/V	0.7705	likely_pathogenic	0.7829	pathogenic	-1.032	Destabilizing	0.993	D	0.765	deleterious	None	None	None	None	N
C/W	0.9756	likely_pathogenic	0.9788	pathogenic	-1.446	Destabilizing	1.0	D	0.841	deleterious	N	0.481107784	None	None	N
C/Y	0.9303	likely_pathogenic	0.9377	pathogenic	-1.25	Destabilizing	0.999	D	0.853	deleterious	N	0.481107784	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.