Submissions for variant NM_020461.4(TUBGCP6):c.5275_5285del (p.Pro1759fs)

dbSNP: rs757636489

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001234815	SCV001407475	uncertain significance	not provided	2022-10-18	criteria provided, single submitter	clinical testing	This sequence change results in a frameshift in the TUBGCP6 gene (p.Pro1759Alafs*68). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 61 amino acid(s) of the TUBGCP6 protein and extend the protein by 6 additional amino acid residues. This variant is present in population databases (rs757636489, gnomAD 0.01%). This variant has not been reported in the literature in individuals affected with TUBGCP6-related conditions. ClinVar contains an entry for this variant (Variation ID: 961164). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx	RCV001234815	SCV001823509	uncertain significance	not provided	2020-11-13	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation as the last 61 amino acids are replaced with 67 different amino acids, although loss-of-function variants have not been reported downstream of this position in the protein; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics	RCV002563817	SCV003687666	uncertain significance	Inborn genetic diseases	2022-06-28	criteria provided, single submitter	clinical testing	Not expected to trigger nonsense-mediated mRNA decay Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital	RCV003473806	SCV004190198	likely pathogenic	Microcephaly and chorioretinopathy 1	2023-12-25	criteria provided, single submitter	clinical testing	Loss of functions variants are known to cause disease as the disease mechanism [PVS1]. This variant is present in population database with an allele frequency of 0.009% (gnomAD). This heterozygous 11 base deletion found in a compound heterozygous state along with a long ~405 base deletion in 2 similarly afftected individuals of the same family.