TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22488	67687;67688;67689	chr2:178579735;178579734;178579733	chr2:179444462;179444461;179444460
N2AB	20847	62764;62765;62766	chr2:178579735;178579734;178579733	chr2:179444462;179444461;179444460
N2A	19920	59983;59984;59985	chr2:178579735;178579734;178579733	chr2:179444462;179444461;179444460
N2B	13423	40492;40493;40494	chr2:178579735;178579734;178579733	chr2:179444462;179444461;179444460
Novex-1	13548	40867;40868;40869	chr2:178579735;178579734;178579733	chr2:179444462;179444461;179444460
Novex-2	13615	41068;41069;41070	chr2:178579735;178579734;178579733	chr2:179444462;179444461;179444460
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTT
• RefSeq wild type template codon: CAA
• Domain: Fn3-51
• Domain position: 38
• Structural Position: 40
• Q(SASA): 0.0527
• 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
V/I	rs1553622498	None	0.835	N	0.428	0.14	0.53099781502	gnomAD-4.0.0	1.20032E-06	None	None	None	None	N	None	6.33473E-05	0	None	0	0	None	0	0	0	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
V/A	0.5755	likely_pathogenic	0.513	ambiguous	-2.365	Highly Destabilizing	0.954	D	0.604	neutral	N	0.513168788	None	None	N
V/C	0.9483	likely_pathogenic	0.9223	pathogenic	-1.989	Destabilizing	1.0	D	0.753	deleterious	None	None	None	None	N
V/D	0.9957	likely_pathogenic	0.9952	pathogenic	-3.444	Highly Destabilizing	0.998	D	0.887	deleterious	N	0.513929257	None	None	N
V/E	0.9879	likely_pathogenic	0.9864	pathogenic	-3.148	Highly Destabilizing	0.999	D	0.832	deleterious	None	None	None	None	N
V/F	0.8479	likely_pathogenic	0.7797	pathogenic	-1.357	Destabilizing	0.989	D	0.743	deleterious	N	0.513675767	None	None	N
V/G	0.869	likely_pathogenic	0.8392	pathogenic	-2.965	Highly Destabilizing	0.998	D	0.829	deleterious	N	0.513929257	None	None	N
V/H	0.997	likely_pathogenic	0.9957	pathogenic	-2.883	Highly Destabilizing	1.0	D	0.869	deleterious	None	None	None	None	N
V/I	0.1051	likely_benign	0.0923	benign	-0.634	Destabilizing	0.835	D	0.428	neutral	N	0.442410536	None	None	N
V/K	0.9897	likely_pathogenic	0.9886	pathogenic	-2.058	Highly Destabilizing	0.999	D	0.801	deleterious	None	None	None	None	N
V/L	0.379	ambiguous	0.2781	benign	-0.634	Destabilizing	0.031	N	0.316	neutral	N	0.411554485	None	None	N
V/M	0.5471	ambiguous	0.4264	ambiguous	-0.863	Destabilizing	0.991	D	0.647	neutral	None	None	None	None	N
V/N	0.9892	likely_pathogenic	0.9855	pathogenic	-2.655	Highly Destabilizing	0.999	D	0.891	deleterious	None	None	None	None	N
V/P	0.9893	likely_pathogenic	0.989	pathogenic	-1.19	Destabilizing	0.999	D	0.857	deleterious	None	None	None	None	N
V/Q	0.986	likely_pathogenic	0.983	pathogenic	-2.351	Highly Destabilizing	0.999	D	0.867	deleterious	None	None	None	None	N
V/R	0.9799	likely_pathogenic	0.9791	pathogenic	-2.038	Highly Destabilizing	0.999	D	0.89	deleterious	None	None	None	None	N
V/S	0.9366	likely_pathogenic	0.9136	pathogenic	-3.197	Highly Destabilizing	0.999	D	0.781	deleterious	None	None	None	None	N
V/T	0.7043	likely_pathogenic	0.6543	pathogenic	-2.747	Highly Destabilizing	0.985	D	0.591	neutral	None	None	None	None	N
V/W	0.9966	likely_pathogenic	0.9949	pathogenic	-2.01	Highly Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
V/Y	0.9895	likely_pathogenic	0.9839	pathogenic	-1.648	Destabilizing	0.999	D	0.742	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.