TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	19300	58123;58124;58125	chr2:178594596;178594595;178594594	chr2:179459323;179459322;179459321
N2AB	17659	53200;53201;53202	chr2:178594596;178594595;178594594	chr2:179459323;179459322;179459321
N2A	16732	50419;50420;50421	chr2:178594596;178594595;178594594	chr2:179459323;179459322;179459321
N2B	10235	30928;30929;30930	chr2:178594596;178594595;178594594	chr2:179459323;179459322;179459321
Novex-1	10360	31303;31304;31305	chr2:178594596;178594595;178594594	chr2:179459323;179459322;179459321
Novex-2	10427	31504;31505;31506	chr2:178594596;178594595;178594594	chr2:179459323;179459322;179459321
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: T
• RefSeq wild type transcript codon: ACT
• RefSeq wild type template codon: TGA
• Domain: Fn3-28
• Domain position: 17
• Structural Position: 19
• Q(SASA): 0.1784
• 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
T/A	rs1303630569	-0.858	0.012	N	0.347	0.118	0.119812018005	gnomAD-2.1.1	8.07E-06	None	None	None	None	N	None	0	0	None	0	0	None	6.57E-05	None	0	0	0
T/A	rs1303630569	-0.858	0.012	N	0.347	0.118	0.119812018005	gnomAD-4.0.0	4.78292E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	4.31047E-05	0
T/N	rs979451740	None	0.062	N	0.495	0.123	0.270889551736	gnomAD-4.0.0	2.73922E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	6.9541E-04	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
T/A	0.0892	likely_benign	0.1007	benign	-0.709	Destabilizing	0.012	N	0.347	neutral	N	0.474210737	None	None	N
T/C	0.2506	likely_benign	0.3017	benign	-0.96	Destabilizing	0.824	D	0.685	prob.neutral	None	None	None	None	N
T/D	0.3961	ambiguous	0.4226	ambiguous	-1.859	Destabilizing	0.081	N	0.539	neutral	None	None	None	None	N
T/E	0.3266	likely_benign	0.3426	ambiguous	-1.788	Destabilizing	0.081	N	0.541	neutral	None	None	None	None	N
T/F	0.2189	likely_benign	0.2548	benign	-0.79	Destabilizing	0.555	D	0.678	prob.neutral	None	None	None	None	N
T/G	0.2293	likely_benign	0.2721	benign	-0.992	Destabilizing	0.035	N	0.461	neutral	None	None	None	None	N
T/H	0.2211	likely_benign	0.2489	benign	-1.319	Destabilizing	0.555	D	0.687	prob.neutral	None	None	None	None	N
T/I	0.3037	likely_benign	0.34	ambiguous	-0.03	Destabilizing	0.117	N	0.648	neutral	N	0.482564187	None	None	N
T/K	0.3567	ambiguous	0.3816	ambiguous	-0.829	Destabilizing	0.081	N	0.541	neutral	None	None	None	None	N
T/L	0.1452	likely_benign	0.1604	benign	-0.03	Destabilizing	0.149	N	0.541	neutral	None	None	None	None	N
T/M	0.1002	likely_benign	0.1004	benign	0.122	Stabilizing	0.791	D	0.691	prob.neutral	None	None	None	None	N
T/N	0.1341	likely_benign	0.1613	benign	-1.28	Destabilizing	0.062	N	0.495	neutral	N	0.502570774	None	None	N
T/P	0.9612	likely_pathogenic	0.951	pathogenic	-0.225	Destabilizing	0.117	N	0.625	neutral	N	0.494085076	None	None	N
T/Q	0.2827	likely_benign	0.3016	benign	-1.423	Destabilizing	0.38	N	0.663	neutral	None	None	None	None	N
T/R	0.3067	likely_benign	0.3225	benign	-0.636	Destabilizing	0.38	N	0.654	neutral	None	None	None	None	N
T/S	0.073	likely_benign	0.0797	benign	-1.306	Destabilizing	None	N	0.155	neutral	N	0.361514375	None	None	N
T/V	0.2121	likely_benign	0.2408	benign	-0.225	Destabilizing	0.149	N	0.491	neutral	None	None	None	None	N
T/W	0.5586	ambiguous	0.599	pathogenic	-0.906	Destabilizing	0.935	D	0.701	prob.neutral	None	None	None	None	N
T/Y	0.2167	likely_benign	0.2642	benign	-0.526	Destabilizing	0.555	D	0.692	prob.neutral	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.