Submissions for variant NM_014639.4(SKIC3):c.3808C>G (p.Pro1270Ala)

gnomAD frequency: 0.00018  dbSNP: rs146627706

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000493753	SCV000582800	uncertain significance	not provided	2017-05-18	criteria provided, single submitter	clinical testing	The P1270A variant in the TTC37 gene has been reported previously in association with autosomal recessive trichohepatoenteric syndrome when present in the homozygous state (Fabre et al., 2011; Busoni et al., 2016). The P1270A variant is observed in 50/16314 (0.3%) alleles from individuals of South Asian background in large population cohorts with one homozygous individual reported (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The P1270A variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. This substitution occurs at a position that is conserved across species. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. We interpret P1270A as a variant of uncertain significance.
Fulgent Genetics, Fulgent Genetics	RCV000765861	SCV000897257	uncertain significance	Trichohepatoenteric syndrome 1	2018-10-31	criteria provided, single submitter	clinical testing
Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital	RCV000765861	SCV001984410	uncertain significance	Trichohepatoenteric syndrome 1	2020-07-21	criteria provided, single submitter	clinical testing
Invitae	RCV000493753	SCV002338461	likely benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago	RCV000765861	SCV002496015	uncertain significance	Trichohepatoenteric syndrome 1	2022-01-27	criteria provided, single submitter	clinical testing	TTC37 NM_014639.3 exon 37 p.Pro1270Ala (c.3808C>G): This variant has been reported in the literature in at least 2 individuals with trichohepatoenteric syndrome (Fabre 2011 PMID:21120949, Busoni 2017 PMID:28027214, Vely 2018 PMID:29868001). This variant is present in 0.02% (19/68016) of European alleles in the Genome Aggregation Database (https://gnomad.broadinstitute.org/variant/5-95491031-G-C?dataset=gnomad_r3). This variant is present in ClinVar (Variation ID:430077). Evolutionary conservation suggests that this variant may impact the protein; computational predictive tools suggest that this variant may not impact the protein. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000493753	SCV001740208	uncertain significance	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000493753	SCV001808190	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000493753	SCV001967571	uncertain significance	not provided		no assertion criteria provided	clinical testing