TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	16318	49177;49178;49179	chr2:178614562;178614561;178614560	chr2:179479289;179479288;179479287
N2AB	14677	44254;44255;44256	chr2:178614562;178614561;178614560	chr2:179479289;179479288;179479287
N2A	13750	41473;41474;41475	chr2:178614562;178614561;178614560	chr2:179479289;179479288;179479287
N2B	7253	21982;21983;21984	chr2:178614562;178614561;178614560	chr2:179479289;179479288;179479287
Novex-1	7378	22357;22358;22359	chr2:178614562;178614561;178614560	chr2:179479289;179479288;179479287
Novex-2	7445	22558;22559;22560	chr2:178614562;178614561;178614560	chr2:179479289;179479288;179479287
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATT
• RefSeq wild type template codon: TAA
• Domain: Ig-110
• Domain position: 57
• Structural Position: 140
• Q(SASA): 0.1186
• 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
I/L	rs962564634	None	0.889	D	0.415	0.489	0.721054117171	gnomAD-3.1.2	1.32E-05	None	None	None	None	N	None	0	0	0	0	0	None	0	0	2.95E-05	0	0
I/L	rs962564634	None	0.889	D	0.415	0.489	0.721054117171	gnomAD-4.0.0	1.31709E-05	None	None	None	None	N	None	0	0	None	0	0	None	0	0	2.94594E-05	0	0
I/T	rs72677243	-2.811	0.989	D	0.753	0.748	None	gnomAD-2.1.1	1.17164E-03	None	None	None	None	N	None	1.24131E-04	1.10726E-03	None	1.02693E-02	5.2E-05	None	4.25142E-04	None	8.01E-05	1.19961E-03	1.41084E-03
I/T	rs72677243	-2.811	0.989	D	0.753	0.748	None	gnomAD-3.1.2	9.55242E-04	None	None	None	None	N	None	2.41663E-04	7.8854E-04	0	1.09763E-02	0	None	0	9.49367E-03	1.10463E-03	4.16667E-04	2.39693E-03
I/T	rs72677243	-2.811	0.989	D	0.753	0.748	None	1000 genomes	3.99361E-04	None	None	None	None	N	None	8E-04	1.4E-03	None	None	0	0	None	None	None	0	None
I/T	rs72677243	-2.811	0.989	D	0.753	0.748	None	gnomAD-4.0.0	1.02707E-03	None	None	None	None	N	None	2.40327E-04	1.08579E-03	None	9.70907E-03	0	None	4.69087E-05	1.65344E-03	9.66821E-04	5.82341E-04	1.28201E-03
I/V	rs962564634	-1.651	0.333	D	0.235	0.358	0.678242657409	gnomAD-2.1.1	4.04E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.27E-05	None	0	0	0
I/V	rs962564634	-1.651	0.333	D	0.235	0.358	0.678242657409	gnomAD-4.0.0	3.42363E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	1.79979E-06	3.47987E-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
I/A	0.9188	likely_pathogenic	0.9192	pathogenic	-2.792	Highly Destabilizing	0.992	D	0.685	prob.neutral	None	None	None	None	N
I/C	0.9614	likely_pathogenic	0.9542	pathogenic	-2.322	Highly Destabilizing	1.0	D	0.736	prob.delet.	None	None	None	None	N
I/D	0.9986	likely_pathogenic	0.9985	pathogenic	-3.021	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
I/E	0.996	likely_pathogenic	0.9956	pathogenic	-2.859	Highly Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
I/F	0.6523	likely_pathogenic	0.5986	pathogenic	-1.778	Destabilizing	0.998	D	0.731	prob.delet.	D	0.650179428	None	None	N
I/G	0.9949	likely_pathogenic	0.9944	pathogenic	-3.278	Highly Destabilizing	1.0	D	0.861	deleterious	None	None	None	None	N
I/H	0.9916	likely_pathogenic	0.9908	pathogenic	-2.49	Highly Destabilizing	1.0	D	0.824	deleterious	None	None	None	None	N
I/K	0.9886	likely_pathogenic	0.9888	pathogenic	-2.256	Highly Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
I/L	0.3612	ambiguous	0.3372	benign	-1.41	Destabilizing	0.889	D	0.415	neutral	D	0.598196869	None	None	N
I/M	0.3301	likely_benign	0.3102	benign	-1.41	Destabilizing	0.998	D	0.684	prob.neutral	D	0.691398815	None	None	N
I/N	0.9797	likely_pathogenic	0.9777	pathogenic	-2.475	Highly Destabilizing	0.999	D	0.852	deleterious	D	0.809461466	None	None	N
I/P	0.9979	likely_pathogenic	0.9982	pathogenic	-1.85	Destabilizing	1.0	D	0.848	deleterious	None	None	None	None	N
I/Q	0.9904	likely_pathogenic	0.9899	pathogenic	-2.468	Highly Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
I/R	0.9818	likely_pathogenic	0.9818	pathogenic	-1.732	Destabilizing	1.0	D	0.857	deleterious	None	None	None	None	N
I/S	0.9666	likely_pathogenic	0.965	pathogenic	-3.187	Highly Destabilizing	0.998	D	0.836	deleterious	D	0.77478352	None	None	N
I/T	0.9089	likely_pathogenic	0.9123	pathogenic	-2.89	Highly Destabilizing	0.989	D	0.753	deleterious	D	0.809679107	None	None	N
I/V	0.0992	likely_benign	0.1011	benign	-1.85	Destabilizing	0.333	N	0.235	neutral	D	0.547397643	None	None	N
I/W	0.9906	likely_pathogenic	0.9895	pathogenic	-2.037	Highly Destabilizing	1.0	D	0.821	deleterious	None	None	None	None	N
I/Y	0.9696	likely_pathogenic	0.9637	pathogenic	-1.834	Destabilizing	1.0	D	0.739	prob.delet.	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.