TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	24231	72916;72917;72918	chr2:178573441;178573440;178573439	chr2:179438168;179438167;179438166
N2AB	22590	67993;67994;67995	chr2:178573441;178573440;178573439	chr2:179438168;179438167;179438166
N2A	21663	65212;65213;65214	chr2:178573441;178573440;178573439	chr2:179438168;179438167;179438166
N2B	15166	45721;45722;45723	chr2:178573441;178573440;178573439	chr2:179438168;179438167;179438166
Novex-1	15291	46096;46097;46098	chr2:178573441;178573440;178573439	chr2:179438168;179438167;179438166
Novex-2	15358	46297;46298;46299	chr2:178573441;178573440;178573439	chr2:179438168;179438167;179438166
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: V
• RefSeq wild type transcript codon: GTG
• RefSeq wild type template codon: CAC
• Domain: Fn3-64
• Domain position: 10
• Structural Position: 12
• Q(SASA): 0.1959
• 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/L	None	None	0.898	N	0.501	0.27	0.429552544315	gnomAD-4.0.0	7.32387E-07	None	None	None	None	N	None	3.306E-05	0	None	0	0	None	0	0	0	0	0
V/M	None	None	0.993	N	0.803	0.41	0.519946186488	gnomAD-4.0.0	7.32387E-07	None	None	None	None	N	None	3.306E-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	0.4408	ambiguous	0.3878	ambiguous	-1.68	Destabilizing	0.977	D	0.542	neutral	N	0.509419388	None	None	N
V/C	0.9171	likely_pathogenic	0.9013	pathogenic	-1.089	Destabilizing	1.0	D	0.818	deleterious	None	None	None	None	N
V/D	0.9836	likely_pathogenic	0.975	pathogenic	-2.021	Highly Destabilizing	0.999	D	0.897	deleterious	None	None	None	None	N
V/E	0.9744	likely_pathogenic	0.9618	pathogenic	-1.819	Destabilizing	0.999	D	0.891	deleterious	N	0.512802124	None	None	N
V/F	0.775	likely_pathogenic	0.704	pathogenic	-1.012	Destabilizing	0.995	D	0.873	deleterious	None	None	None	None	N
V/G	0.7404	likely_pathogenic	0.6827	pathogenic	-2.202	Highly Destabilizing	0.999	D	0.889	deleterious	D	0.545857082	None	None	N
V/H	0.9938	likely_pathogenic	0.9894	pathogenic	-1.954	Destabilizing	1.0	D	0.891	deleterious	None	None	None	None	N
V/I	0.0973	likely_benign	0.0935	benign	-0.243	Destabilizing	0.15	N	0.307	neutral	None	None	None	None	N
V/K	0.9878	likely_pathogenic	0.9802	pathogenic	-1.264	Destabilizing	0.998	D	0.895	deleterious	None	None	None	None	N
V/L	0.7085	likely_pathogenic	0.6397	pathogenic	-0.243	Destabilizing	0.898	D	0.501	neutral	N	0.477475305	None	None	N
V/M	0.6296	likely_pathogenic	0.5453	ambiguous	-0.218	Destabilizing	0.993	D	0.803	deleterious	N	0.509813156	None	None	N
V/N	0.9522	likely_pathogenic	0.9262	pathogenic	-1.515	Destabilizing	0.999	D	0.911	deleterious	None	None	None	None	N
V/P	0.8141	likely_pathogenic	0.7776	pathogenic	-0.692	Destabilizing	0.999	D	0.903	deleterious	None	None	None	None	N
V/Q	0.9838	likely_pathogenic	0.9734	pathogenic	-1.378	Destabilizing	0.999	D	0.907	deleterious	None	None	None	None	N
V/R	0.9798	likely_pathogenic	0.9689	pathogenic	-1.151	Destabilizing	0.999	D	0.91	deleterious	None	None	None	None	N
V/S	0.8415	likely_pathogenic	0.7841	pathogenic	-2.143	Highly Destabilizing	0.998	D	0.887	deleterious	None	None	None	None	N
V/T	0.7753	likely_pathogenic	0.7166	pathogenic	-1.79	Destabilizing	0.983	D	0.695	prob.neutral	None	None	None	None	N
V/W	0.996	likely_pathogenic	0.9925	pathogenic	-1.509	Destabilizing	1.0	D	0.859	deleterious	None	None	None	None	N
V/Y	0.9715	likely_pathogenic	0.9553	pathogenic	-1.063	Destabilizing	0.999	D	0.873	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.