TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	10026	30301;30302;30303	chr2:178704294;178704293;178704292	chr2:179569021;179569020;179569019
N2AB	9709	29350;29351;29352	chr2:178704294;178704293;178704292	chr2:179569021;179569020;179569019
N2A	8782	26569;26570;26571	chr2:178704294;178704293;178704292	chr2:179569021;179569020;179569019
N2B	None	None	chr2:None	chr2:None
Novex-1	None	None	chr2:None	chr2:None
Novex-2	None	None	chr2:None	chr2:None
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: R
• RefSeq wild type transcript codon: AGA
• RefSeq wild type template codon: TCT
• Domain: Ig-85
• Domain position: 38
• Structural Position: 55
• Q(SASA): 0.47
• 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
R/T	rs1327825232	None	0.324	None	0.34	0.144	0.376745185316	gnomAD-4.0.0	6.15722E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	8.09454E-06	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
R/A	0.5155	ambiguous	0.5711	pathogenic	0.091	Stabilizing	0.116	N	0.381	neutral	None	None	None	None	N
R/C	0.3686	ambiguous	0.3765	ambiguous	-0.127	Destabilizing	0.981	D	0.374	neutral	None	None	None	None	N
R/D	0.7409	likely_pathogenic	0.7772	pathogenic	-0.098	Destabilizing	0.241	N	0.389	neutral	None	None	None	None	N
R/E	0.3677	ambiguous	0.4055	ambiguous	-0.038	Destabilizing	0.008	N	0.195	neutral	None	None	None	None	N
R/F	0.679	likely_pathogenic	0.7101	pathogenic	-0.173	Destabilizing	0.932	D	0.366	neutral	None	None	None	None	N
R/G	0.4153	ambiguous	0.4735	ambiguous	-0.087	Destabilizing	0.324	N	0.391	neutral	None	None	None	None	N
R/H	0.1451	likely_benign	0.1418	benign	-0.614	Destabilizing	0.818	D	0.31	neutral	None	None	None	None	N
R/I	0.2781	likely_benign	0.2744	benign	0.518	Stabilizing	0.773	D	0.38	neutral	None	None	None	None	N
R/K	0.0969	likely_benign	0.112	benign	-0.005	Destabilizing	None	N	0.159	neutral	None	None	None	None	N
R/L	0.3644	ambiguous	0.3815	ambiguous	0.518	Stabilizing	0.388	N	0.386	neutral	None	None	None	None	N
R/M	0.3125	likely_benign	0.3335	benign	0.038	Stabilizing	0.932	D	0.335	neutral	None	None	None	None	N
R/N	0.5655	likely_pathogenic	0.624	pathogenic	0.132	Stabilizing	0.388	N	0.302	neutral	None	None	None	None	N
R/P	0.9638	likely_pathogenic	0.9718	pathogenic	0.396	Stabilizing	0.818	D	0.363	neutral	None	None	None	None	N
R/Q	0.1125	likely_benign	0.1163	benign	0.078	Stabilizing	0.241	N	0.329	neutral	None	None	None	None	N
R/S	0.5662	likely_pathogenic	0.6374	pathogenic	-0.136	Destabilizing	0.193	N	0.368	neutral	None	None	None	None	N
R/T	0.3106	likely_benign	0.3419	ambiguous	0.051	Stabilizing	0.324	N	0.34	neutral	None	None	None	None	N
R/V	0.3795	ambiguous	0.4018	ambiguous	0.396	Stabilizing	0.388	N	0.399	neutral	None	None	None	None	N
R/W	0.3217	likely_benign	0.3473	ambiguous	-0.3	Destabilizing	0.981	D	0.415	neutral	None	None	None	None	N
R/Y	0.552	ambiguous	0.5782	pathogenic	0.124	Stabilizing	0.932	D	0.359	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.