Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000338433 | SCV000402618 | benign | White sponge nevus 2 | 2018-01-13 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. |
| Ambry Genetics | RCV002522953 | SCV003545348 | uncertain significance | Inborn genetic diseases | 2022-06-09 | criteria provided, single submitter | clinical testing | The c.509C>G (p.T170S) alteration is located in exon 2 (coding exon 2) of the KRT13 gene. This alteration results from a C to G substitution at nucleotide position 509, causing the threonine (T) at amino acid position 170 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. |
| Breakthrough Genomics, |
RCV001357960 | SCV005247606 | benign | not provided | criteria provided, single submitter | not provided | ||
| Department of Pathology and Laboratory Medicine, |
RCV001357960 | SCV001553574 | likely benign | not provided | no assertion criteria provided | clinical testing |  The KRT13 p.T170S variant was not identified in the literature but was identified in dbSNP (ID: rs148102980) and ClinVar (classified as likely benign by Illumina Clinical Services Laboratory for the associated condition White Sponge Nevus of Cannon). The variant was identified in control databases in 181 of 282822 chromosomes at a frequency of 0.00064 increasing the likelihood this could be a low frequency benign variant (Genome Aggregation Database March 6, 2019, v2.1.1). The variant was observed in the following populations: European (non-Finnish) in 172 of 129152 chromosomes (freq: 0.001332), Other in 4 of 7226 chromosomes (freq: 0.000554) and African in 5 of 24954 chromosomes (freq: 0.0002), but was not observed in the Latino, Ashkenazi Jewish, East Asian, European (Finnish), or South Asian populations. The p.T170 residue is conserved in mammals and computational analyses (PolyPhen-2, SIFT, MutationTaster, Revel, FATHMM, MetaLR, DANN) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. The variant occurs outside of the splicing consensus sequence and in silico or computational prediction software programs (Splice AI exome) do not predict a difference in splicing. In summary, based on the above information the clinical significance of this variant cannot be determined with certainty at this time although we would lean towards a more benign role for this variant. This variant is classified as likely benign. |