TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35488	106687;106688;106689	chr2:178530029;178530028;178530027	chr2:179394756;179394755;179394754
N2AB	33847	101764;101765;101766	chr2:178530029;178530028;178530027	chr2:179394756;179394755;179394754
N2A	32920	98983;98984;98985	chr2:178530029;178530028;178530027	chr2:179394756;179394755;179394754
N2B	26423	79492;79493;79494	chr2:178530029;178530028;178530027	chr2:179394756;179394755;179394754
Novex-1	26548	79867;79868;79869	chr2:178530029;178530028;178530027	chr2:179394756;179394755;179394754
Novex-2	26615	80068;80069;80070	chr2:178530029;178530028;178530027	chr2:179394756;179394755;179394754
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: G
• RefSeq wild type transcript codon: GGA
• RefSeq wild type template codon: CCT
• Domain: Ig-166
• Domain position: 69
• Structural Position: 152
• Q(SASA): 0.1348
• 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
G/R	rs1478637421	-0.598	1.0	D	0.837	0.725	0.844932034729	gnomAD-2.1.1	4.08E-06	None	None	None	None	N	None	0	0	None	0	0	None	3.43E-05	None	0	0	0
G/R	rs1478637421	-0.598	1.0	D	0.837	0.725	0.844932034729	gnomAD-4.0.0	1.60066E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.46224E-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
G/A	0.3234	likely_benign	0.3083	benign	-0.647	Destabilizing	0.999	D	0.693	prob.neutral	D	0.545913315	None	None	N
G/C	0.6903	likely_pathogenic	0.6879	pathogenic	-0.869	Destabilizing	1.0	D	0.779	deleterious	None	None	None	None	N
G/D	0.7824	likely_pathogenic	0.7653	pathogenic	-0.936	Destabilizing	1.0	D	0.855	deleterious	None	None	None	None	N
G/E	0.8194	likely_pathogenic	0.8091	pathogenic	-0.951	Destabilizing	1.0	D	0.855	deleterious	D	0.639050624	None	None	N
G/F	0.9343	likely_pathogenic	0.9376	pathogenic	-0.895	Destabilizing	1.0	D	0.813	deleterious	None	None	None	None	N
G/H	0.9214	likely_pathogenic	0.9212	pathogenic	-1.344	Destabilizing	1.0	D	0.771	deleterious	None	None	None	None	N
G/I	0.8532	likely_pathogenic	0.8577	pathogenic	-0.118	Destabilizing	1.0	D	0.814	deleterious	None	None	None	None	N
G/K	0.9236	likely_pathogenic	0.9218	pathogenic	-1.079	Destabilizing	1.0	D	0.845	deleterious	None	None	None	None	N
G/L	0.8853	likely_pathogenic	0.884	pathogenic	-0.118	Destabilizing	1.0	D	0.817	deleterious	None	None	None	None	N
G/M	0.9266	likely_pathogenic	0.9257	pathogenic	-0.142	Destabilizing	1.0	D	0.749	deleterious	None	None	None	None	N
G/N	0.8164	likely_pathogenic	0.8094	pathogenic	-0.839	Destabilizing	1.0	D	0.862	deleterious	None	None	None	None	N
G/P	0.9894	likely_pathogenic	0.9908	pathogenic	-0.251	Destabilizing	1.0	D	0.851	deleterious	None	None	None	None	N
G/Q	0.8599	likely_pathogenic	0.8582	pathogenic	-0.934	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
G/R	0.826	likely_pathogenic	0.8178	pathogenic	-0.898	Destabilizing	1.0	D	0.837	deleterious	D	0.63884882	None	None	N
G/S	0.2305	likely_benign	0.2191	benign	-1.183	Destabilizing	1.0	D	0.853	deleterious	None	None	None	None	N
G/T	0.6634	likely_pathogenic	0.6669	pathogenic	-1.099	Destabilizing	1.0	D	0.856	deleterious	None	None	None	None	N
G/V	0.7602	likely_pathogenic	0.7577	pathogenic	-0.251	Destabilizing	1.0	D	0.821	deleterious	D	0.639050624	None	None	N
G/W	0.9181	likely_pathogenic	0.9268	pathogenic	-1.332	Destabilizing	1.0	D	0.784	deleterious	None	None	None	None	N
G/Y	0.926	likely_pathogenic	0.9256	pathogenic	-0.857	Destabilizing	1.0	D	0.797	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.