TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	17933	54022;54023;54024	chr2:178605498;178605497;178605496	chr2:179470225;179470224;179470223
N2AB	16292	49099;49100;49101	chr2:178605498;178605497;178605496	chr2:179470225;179470224;179470223
N2A	15365	46318;46319;46320	chr2:178605498;178605497;178605496	chr2:179470225;179470224;179470223
N2B	8868	26827;26828;26829	chr2:178605498;178605497;178605496	chr2:179470225;179470224;179470223
Novex-1	8993	27202;27203;27204	chr2:178605498;178605497;178605496	chr2:179470225;179470224;179470223
Novex-2	9060	27403;27404;27405	chr2:178605498;178605497;178605496	chr2:179470225;179470224;179470223
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: Y
• RefSeq wild type transcript codon: TAT
• RefSeq wild type template codon: ATA
• Domain: Fn3-18
• Domain position: 72
• Structural Position: 104
• Q(SASA): 0.0595
• 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
Y/C	rs1271497242	None	1.0	D	0.866	0.853	0.916892032025	gnomAD-4.0.0	3.18885E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	2.86993E-05	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
Y/A	0.9878	likely_pathogenic	0.984	pathogenic	-3.294	Highly Destabilizing	0.998	D	0.839	deleterious	None	None	None	None	N
Y/C	0.8729	likely_pathogenic	0.8432	pathogenic	-1.884	Destabilizing	1.0	D	0.866	deleterious	D	0.625109976	None	None	N
Y/D	0.9916	likely_pathogenic	0.9913	pathogenic	-3.81	Highly Destabilizing	1.0	D	0.882	deleterious	D	0.662488485	None	None	N
Y/E	0.9967	likely_pathogenic	0.9962	pathogenic	-3.6	Highly Destabilizing	1.0	D	0.873	deleterious	None	None	None	None	N
Y/F	0.2187	likely_benign	0.202	benign	-1.228	Destabilizing	0.434	N	0.528	neutral	D	0.583361418	None	None	N
Y/G	0.9802	likely_pathogenic	0.9779	pathogenic	-3.704	Highly Destabilizing	1.0	D	0.876	deleterious	None	None	None	None	N
Y/H	0.9206	likely_pathogenic	0.9122	pathogenic	-2.376	Highly Destabilizing	1.0	D	0.811	deleterious	D	0.64623696	None	None	N
Y/I	0.9628	likely_pathogenic	0.9464	pathogenic	-1.915	Destabilizing	0.999	D	0.82	deleterious	None	None	None	None	N
Y/K	0.9975	likely_pathogenic	0.9968	pathogenic	-2.392	Highly Destabilizing	1.0	D	0.872	deleterious	None	None	None	None	N
Y/L	0.9067	likely_pathogenic	0.8596	pathogenic	-1.915	Destabilizing	0.994	D	0.777	deleterious	None	None	None	None	N
Y/M	0.9631	likely_pathogenic	0.9408	pathogenic	-1.641	Destabilizing	1.0	D	0.839	deleterious	None	None	None	None	N
Y/N	0.9565	likely_pathogenic	0.9502	pathogenic	-3.214	Highly Destabilizing	1.0	D	0.87	deleterious	D	0.662286681	None	None	N
Y/P	0.9987	likely_pathogenic	0.9987	pathogenic	-2.393	Highly Destabilizing	1.0	D	0.889	deleterious	None	None	None	None	N
Y/Q	0.995	likely_pathogenic	0.9933	pathogenic	-2.959	Highly Destabilizing	1.0	D	0.831	deleterious	None	None	None	None	N
Y/R	0.9907	likely_pathogenic	0.9884	pathogenic	-2.139	Highly Destabilizing	1.0	D	0.86	deleterious	None	None	None	None	N
Y/S	0.9766	likely_pathogenic	0.9706	pathogenic	-3.506	Highly Destabilizing	1.0	D	0.868	deleterious	D	0.662488485	None	None	N
Y/T	0.9898	likely_pathogenic	0.9874	pathogenic	-3.178	Highly Destabilizing	1.0	D	0.868	deleterious	None	None	None	None	N
Y/V	0.9175	likely_pathogenic	0.8881	pathogenic	-2.393	Highly Destabilizing	0.997	D	0.8	deleterious	None	None	None	None	N
Y/W	0.6614	likely_pathogenic	0.6454	pathogenic	-0.538	Destabilizing	1.0	D	0.795	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.