TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	22680	68263;68264;68265	chr2:178578992;178578991;178578990	chr2:179443719;179443718;179443717
N2AB	21039	63340;63341;63342	chr2:178578992;178578991;178578990	chr2:179443719;179443718;179443717
N2A	20112	60559;60560;60561	chr2:178578992;178578991;178578990	chr2:179443719;179443718;179443717
N2B	13615	41068;41069;41070	chr2:178578992;178578991;178578990	chr2:179443719;179443718;179443717
Novex-1	13740	41443;41444;41445	chr2:178578992;178578991;178578990	chr2:179443719;179443718;179443717
Novex-2	13807	41644;41645;41646	chr2:178578992;178578991;178578990	chr2:179443719;179443718;179443717
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: I
• RefSeq wild type transcript codon: ATC
• RefSeq wild type template codon: TAG
• Domain: Fn3-52
• Domain position: 38
• Structural Position: 39
• Q(SASA): 0.2187
• 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/V	rs2047081952	None	None	N	0.281	0.087	0.393006254552	gnomAD-4.0.0	1.59238E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43279E-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	0.8567	likely_pathogenic	0.8251	pathogenic	-2.367	Highly Destabilizing	0.157	N	0.62	neutral	None	None	None	None	N
I/C	0.847	likely_pathogenic	0.8219	pathogenic	-1.91	Destabilizing	0.909	D	0.707	prob.neutral	None	None	None	None	N
I/D	0.9822	likely_pathogenic	0.9741	pathogenic	-2.709	Highly Destabilizing	0.726	D	0.751	deleterious	None	None	None	None	N
I/E	0.9585	likely_pathogenic	0.944	pathogenic	-2.624	Highly Destabilizing	0.726	D	0.746	deleterious	None	None	None	None	N
I/F	0.373	ambiguous	0.3386	benign	-1.582	Destabilizing	0.002	N	0.445	neutral	N	0.488273325	None	None	N
I/G	0.9642	likely_pathogenic	0.9527	pathogenic	-2.762	Highly Destabilizing	0.726	D	0.727	prob.delet.	None	None	None	None	N
I/H	0.8251	likely_pathogenic	0.7872	pathogenic	-1.905	Destabilizing	0.968	D	0.756	deleterious	None	None	None	None	N
I/K	0.8892	likely_pathogenic	0.8441	pathogenic	-1.753	Destabilizing	0.726	D	0.744	deleterious	None	None	None	None	N
I/L	0.2533	likely_benign	0.2597	benign	-1.285	Destabilizing	0.025	N	0.45	neutral	N	0.500874476	None	None	N
I/M	0.2985	likely_benign	0.2715	benign	-1.252	Destabilizing	0.497	N	0.668	neutral	N	0.472520874	None	None	N
I/N	0.7612	likely_pathogenic	0.7214	pathogenic	-1.835	Destabilizing	0.859	D	0.765	deleterious	N	0.510763396	None	None	N
I/P	0.9945	likely_pathogenic	0.9931	pathogenic	-1.622	Destabilizing	0.89	D	0.763	deleterious	None	None	None	None	N
I/Q	0.8734	likely_pathogenic	0.8305	pathogenic	-1.974	Destabilizing	0.89	D	0.76	deleterious	None	None	None	None	N
I/R	0.8083	likely_pathogenic	0.7491	pathogenic	-1.16	Destabilizing	0.726	D	0.765	deleterious	None	None	None	None	N
I/S	0.7235	likely_pathogenic	0.6862	pathogenic	-2.457	Highly Destabilizing	0.497	N	0.693	prob.neutral	N	0.502893274	None	None	N
I/T	0.6212	likely_pathogenic	0.5522	ambiguous	-2.257	Highly Destabilizing	0.124	N	0.663	neutral	N	0.461201367	None	None	N
I/V	0.0873	likely_benign	0.0851	benign	-1.622	Destabilizing	None	N	0.281	neutral	N	0.467820695	None	None	N
I/W	0.9489	likely_pathogenic	0.9247	pathogenic	-1.756	Destabilizing	0.968	D	0.756	deleterious	None	None	None	None	N
I/Y	0.7637	likely_pathogenic	0.7284	pathogenic	-1.544	Destabilizing	0.396	N	0.705	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.