TITINdb

Isoform Positions

Isoform	Protein Position	Transcript Position	Chromosomal Position (HG38)	Chromosomal Position (HG19)
IC	35315	106168;106169;106170	chr2:178530672;178530671;178530670	chr2:179395399;179395398;179395397
N2AB	33674	101245;101246;101247	chr2:178530672;178530671;178530670	chr2:179395399;179395398;179395397
N2A	32747	98464;98465;98466	chr2:178530672;178530671;178530670	chr2:179395399;179395398;179395397
N2B	26250	78973;78974;78975	chr2:178530672;178530671;178530670	chr2:179395399;179395398;179395397
Novex-1	26375	79348;79349;79350	chr2:178530672;178530671;178530670	chr2:179395399;179395398;179395397
Novex-2	26442	79549;79550;79551	chr2:178530672;178530671;178530670	chr2:179395399;179395398;179395397
Novex-3	None	None	chr2:None	chr2:None

Information

• RefSeq wild type amino acid: K
• RefSeq wild type transcript codon: AAA
• RefSeq wild type template codon: TTT
• Domain: Ig-165
• Domain position: 30
• Structural Position: 44
• Q(SASA): 0.0906
• 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
K/T	None	None	0.549	N	0.637	0.301	0.318252033908	gnomAD-4.0.0	1.59086E-06	None	None	None	None	N	None	0	0	None	0	0	None	0	0	0	1.43271E-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
K/A	0.3881	ambiguous	0.3573	ambiguous	0.027	Stabilizing	0.4	N	0.573	neutral	None	None	None	None	N
K/C	0.8585	likely_pathogenic	0.8298	pathogenic	-0.198	Destabilizing	0.992	D	0.712	prob.delet.	None	None	None	None	N
K/D	0.5689	likely_pathogenic	0.5303	ambiguous	0.076	Stabilizing	0.617	D	0.651	neutral	None	None	None	None	N
K/E	0.1596	likely_benign	0.1461	benign	0.074	Stabilizing	0.201	N	0.509	neutral	N	0.468277347	None	None	N
K/F	0.9171	likely_pathogenic	0.9015	pathogenic	-0.235	Destabilizing	0.972	D	0.758	deleterious	None	None	None	None	N
K/G	0.4073	ambiguous	0.3825	ambiguous	-0.153	Destabilizing	0.617	D	0.623	neutral	None	None	None	None	N
K/H	0.5115	ambiguous	0.4721	ambiguous	-0.416	Destabilizing	0.92	D	0.7	prob.neutral	None	None	None	None	N
K/I	0.6176	likely_pathogenic	0.5734	pathogenic	0.419	Stabilizing	0.896	D	0.767	deleterious	N	0.456366842	None	None	N
K/L	0.552	ambiguous	0.5204	ambiguous	0.419	Stabilizing	0.617	D	0.623	neutral	None	None	None	None	N
K/M	0.4011	ambiguous	0.3696	ambiguous	0.225	Stabilizing	0.92	D	0.7	prob.neutral	None	None	None	None	N
K/N	0.4392	ambiguous	0.4047	ambiguous	0.279	Stabilizing	0.549	D	0.608	neutral	N	0.479225059	None	None	N
K/P	0.6939	likely_pathogenic	0.6661	pathogenic	0.316	Stabilizing	0.92	D	0.727	prob.delet.	None	None	None	None	N
K/Q	0.1687	likely_benign	0.1557	benign	0.092	Stabilizing	0.016	N	0.239	neutral	N	0.468450705	None	None	N
K/R	0.0992	likely_benign	0.0928	benign	0.02	Stabilizing	0.001	N	0.122	neutral	N	0.468450705	None	None	N
K/S	0.4103	ambiguous	0.3836	ambiguous	-0.206	Destabilizing	0.617	D	0.55	neutral	None	None	None	None	N
K/T	0.2237	likely_benign	0.2038	benign	-0.066	Destabilizing	0.549	D	0.637	neutral	N	0.423929137	None	None	N
K/V	0.5237	ambiguous	0.4877	ambiguous	0.316	Stabilizing	0.617	D	0.707	prob.neutral	None	None	None	None	N
K/W	0.8896	likely_pathogenic	0.8672	pathogenic	-0.258	Destabilizing	0.992	D	0.721	prob.delet.	None	None	None	None	N
K/Y	0.8429	likely_pathogenic	0.8138	pathogenic	0.104	Stabilizing	0.972	D	0.751	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.